INVESTIGATIONS
• Blood test - General investigations may show anaemia or low platelet count. The peripheral white blood cell count can vary between 50-200 x 10/9 per litre. The peripheral blast count is less than 10% in the chronic phase. You will have a blood test which checks the number and stage of development of all the different types of blood cell. If the blood test shows that leukaemia cells are present, the doctor will want to take a sample of your bone marrow to confirm a diagnosis.
• Bone marrow biopsy – from the hip bone or sternum. Takes around 15-20 minutes. The type of leukaemia present can be diagnosed by identifying the abnormal WBCs. The bone marrow can also be examined to see if the Philadelphia chromosome is present. It can take up to a week to get results.
• Laboratory test – to detect the BRC-ABL Philadelphia chromosome.
Enjoy :)
Friday, June 12, 2009
Signs and SYmptoms
Chronic Myeloid Leukemia
Signs and Symptoms
Patient Presents with:
- Fatigue (caused by the anaemia)
- Low Grade Fevers and Sweats
- Fullness in the abdomen caused by an enlarged spleen
- Weight loss
- Bone pain
- General Weakness (caused by the anaemia)
- Excess bruising or bleeding due to less functional platelets
Signs and Symptoms
Patient Presents with:
- Fatigue (caused by the anaemia)
- Low Grade Fevers and Sweats
- Fullness in the abdomen caused by an enlarged spleen
- Weight loss
- Bone pain
- General Weakness (caused by the anaemia)
- Excess bruising or bleeding due to less functional platelets
what is massive splenomegaly
What is massive splenomegaly?
Splenomegaly is enlargement of the spleen. However, massive splenomegaly is usually defined as a spleen extending into the left lower quadrant or pelvis or spleen which has crossed the midline of the abdomen. Massive spleen is weigh at least 500 to 1000g. Once the spleen is palpable in physical examination, it has usually reached twice its normal size.
Cause of massive splenomegaly:
1. Myeloproliferative disease:
a. Chronic myeloid leukemia
b. Polycythemia vera: clonal expansion of haematopoiesis. Lab findings include increased WBC and platelet counts.
2. Gaucher disease: autosomal recessive lyosomal glycolipid storage disorder due to insufficient acid beta-glucosidase enzyme. This leads to clinical manifestation of hepatosplenomegaly, anemia, thrombocytopenia and bone disease.
3. Lymphoma:
a. Chronic lymphocytic leukemia
b. Hairy cell leukemia: uncommon chronic B-cell lymphopoliferative disease.
c. Thalassemia major: b-Thalassemia major is a hereditary anemia resulting from decreased production of b-globin chains. Decreased b-chain synthesis results in excess free a chains that form insoluble tetramers and precipitate within the RBC, causing increased fragility and cell death.
Thursday, June 11, 2009
Pathophysiology of CML
Pathophysiology of CML
· Due to growth and replication of an abnormal clone
· Philadelphia chromosome
o 9-22 reciprocal translocation
§ ABL – 9
§ BCR - 22
o BCR-ABL gene fusion
§ ABL – tyrosine kinase
§ BCR – break cluster region (normal function unknown)
§ Leads to disregulated tyrosine kinase activity (ABL)
o BCR-ABL fusion protein expressed
§ Increased activity
§ Causes the leukaemia
§ Normally, ABL acts in the nucleus - inhibits the retinoblastoma gene à inhibits cell growth
§ In CML, ABL acts mainly in the cytoplasm à constitutive tyrosine kinase activity – cellular transformation and deregulated growth (inhibition of apoptosis)
· Initially - Expansion of semi-mature granulocytes (Myeloid stem cell line)
o production of immature cells
· Acquisition of additional genetic mutations
o ‘blastic crisis’
o Can cause acute myeloid or acute lymphatic leukaemia
· Due to growth and replication of an abnormal clone
· Philadelphia chromosome
o 9-22 reciprocal translocation
§ ABL – 9
§ BCR - 22
o BCR-ABL gene fusion
§ ABL – tyrosine kinase
§ BCR – break cluster region (normal function unknown)
§ Leads to disregulated tyrosine kinase activity (ABL)
o BCR-ABL fusion protein expressed
§ Increased activity
§ Causes the leukaemia
§ Normally, ABL acts in the nucleus - inhibits the retinoblastoma gene à inhibits cell growth
§ In CML, ABL acts mainly in the cytoplasm à constitutive tyrosine kinase activity – cellular transformation and deregulated growth (inhibition of apoptosis)
· Initially - Expansion of semi-mature granulocytes (Myeloid stem cell line)
o production of immature cells
· Acquisition of additional genetic mutations
o ‘blastic crisis’
o Can cause acute myeloid or acute lymphatic leukaemia
Diagnosis of Chronic Myeloid Leukaemia
Diagnosis of Chronic Myeloid Leukaemia
Usual peripheral blood findings in chronic myeloid leukaemia at diagnosis
* Raised white blood cell count (30-400 x 109/l). Differential shows:
Granulocytes at all stages of development
Increased numbers of basophils and eosinophils
Blast (primitive) cells (maximum 10%)–never present in the blood of normal people
* Haemoglobin concentration may be reduced; red cell morphology is usually unremarkable; nucleated (immature) red cells may be present
* Platelet count may be raised (300-600 x 109/l)\
The diagnosis of chronic myeloid leukaemia in chronic phase can be made from study of the peripheral blood film, but the marrow is usually examined for confirmation.
Marrow examination shows increased cellularity. The distribution of immature leucocytes resembles that seen in the blood film. Red cell production is relatively reduced. Megakaryocytes, the cells giving rise to platelets, are plentiful but may be smaller than usual.
Cytogenetic study of marrow shows the presence of the Ph chromosome in all dividing cells.
The patient's blood concentrations of urea and electrolytes are usually normal at diagnosis, whereas the lactate dehydrogenase is usually raised. Serum urate concentration may be raised.
Sarah
References
http://www.bmj.com/cgi/content/full/314/7081/657
Usual peripheral blood findings in chronic myeloid leukaemia at diagnosis
* Raised white blood cell count (30-400 x 109/l). Differential shows:
Granulocytes at all stages of development
Increased numbers of basophils and eosinophils
Blast (primitive) cells (maximum 10%)–never present in the blood of normal people
* Haemoglobin concentration may be reduced; red cell morphology is usually unremarkable; nucleated (immature) red cells may be present
* Platelet count may be raised (300-600 x 109/l)\
The diagnosis of chronic myeloid leukaemia in chronic phase can be made from study of the peripheral blood film, but the marrow is usually examined for confirmation.
Marrow examination shows increased cellularity. The distribution of immature leucocytes resembles that seen in the blood film. Red cell production is relatively reduced. Megakaryocytes, the cells giving rise to platelets, are plentiful but may be smaller than usual.
Cytogenetic study of marrow shows the presence of the Ph chromosome in all dividing cells.
The patient's blood concentrations of urea and electrolytes are usually normal at diagnosis, whereas the lactate dehydrogenase is usually raised. Serum urate concentration may be raised.
Sarah
References
http://www.bmj.com/cgi/content/full/314/7081/657
Wednesday, June 10, 2009
Complications of CML
At the time of diagnosis, >80% of patients are in chronic phase, which is asymptomatic in many patients.
If CML is left untreated, the natural progression is rapid and fatal, with a median survival of about 3 to 5 years in patients.
As patient progresses into accelerated phase and blast phase, he/she would experience symptoms that often are secondary to splenomegaly: abdominal fullness, pain from splenic infaraction. The spleen may be so enlarged that it may fill the abdominal cavity and extend into the pelvis. Hepatomegaly is also frequently present. Infection and bleeding, which are not common in the chronic phase, are eventually picked up as the disease progresses.
Leukocytosis is a common feature, up to the excess of 300 x 109 /l. The leukocytes are abnormal, with no or severely reduced content of alkaline phosphatise.
The increased numbers of blast cells >30% in blood and bone marrow, marked anaemia and thrombocytopenia are signs of the acute, terminal phase of the disease. This is when the myeloid cells have eventually lost the ability to differentiate, in which clinical features are very close to those of acute leukaemia.
If CML is left untreated, the natural progression is rapid and fatal, with a median survival of about 3 to 5 years in patients.
As patient progresses into accelerated phase and blast phase, he/she would experience symptoms that often are secondary to splenomegaly: abdominal fullness, pain from splenic infaraction. The spleen may be so enlarged that it may fill the abdominal cavity and extend into the pelvis. Hepatomegaly is also frequently present. Infection and bleeding, which are not common in the chronic phase, are eventually picked up as the disease progresses.
Leukocytosis is a common feature, up to the excess of 300 x 109 /l. The leukocytes are abnormal, with no or severely reduced content of alkaline phosphatise.
The increased numbers of blast cells >30% in blood and bone marrow, marked anaemia and thrombocytopenia are signs of the acute, terminal phase of the disease. This is when the myeloid cells have eventually lost the ability to differentiate, in which clinical features are very close to those of acute leukaemia.
Incidence
Incidence vs Prevalence
The "prevalence" of a condition means the number of people who currently have the condition, whereas "incidence" refers to the annual number of people who have a case of the condition.
-----
Incidence: CML has an incidence of around 1–2 cases per 100,000; in
Australia, there are probably more than 200 new cases per year
Prevalence: 1300 prevalent cases/Australia.
Joske, D. J. L. (2008). "Chronic myeloid leukaemia: the evolution of gene-targeted therapy." Medical Journal of Australia 189(5): 277-82.
The "prevalence" of a condition means the number of people who currently have the condition, whereas "incidence" refers to the annual number of people who have a case of the condition.
-----
Incidence: CML has an incidence of around 1–2 cases per 100,000; in
Australia, there are probably more than 200 new cases per year
Prevalence: 1300 prevalent cases/Australia.
Joske, D. J. L. (2008). "Chronic myeloid leukaemia: the evolution of gene-targeted therapy." Medical Journal of Australia 189(5): 277-82.
Monday, June 8, 2009
Definition
Leukemia, chronic myeloid
Chronic myeloid leukemia (CML) is a cancer of blood cells, characterized by replacement of the bone marrow with malignant, leukemic cells. Many of these leukemic cells can be found circulating in the blood and can cause enlargement of the spleen, liver, and other organs.
CML is often suspected on the basis on the complete blood count, which shows increased granulocytes of all types, typically including mature myeloid cells. Basophils andeosinophils are almost universally increased; this feature may help differentiate CML from a leukemoid reaction. A bone marrow biopsy is often performed as part of the evaluation for CML, but bone marrow morphology alone is insufficient to diagnose CML
CML is usually diagnosed by finding a specific chromosomal abnormality called the Philadelphia (Ph) chromosome (see figure), named after the city where it was first recorded. The Ph chromosome is the result of a translocation—or exchange of genetic material—between the long arms of chromosomes 9 and 22 . This exchange brings together two genes: the BCR (breakpoint cluster region) gene on chromosome 22 and the proto-oncogene ABL (Ableson leukemia virus) on chromosome 9. The resulting hybrid gene BCR-ABL codes for a fusion protein with tyrosine kinase activity, which activates signal transduction pathways, leading to uncontrolled cell growth.
Tasks
Tasks
• CML
o Definition - Ari
o Incidence - Nathan
o Eitiology - Rushmi
o S and S - abmu
o Ix - Georgia
o Diagnoses - Me
o Mx - Jacqui
o Marrow transplant - sam
o ComplicationsDillys
o Prognosis - Kylie
o
Task
• What is massive splenomegaly? - Hasif
• Types of anaemia - Steph
o Hypo/normo, hypochromic
o Macro/norma/ chormic cytic
• Why some people can’t donate blood - lional
• CML
o Definition - Ari
o Incidence - Nathan
o Eitiology - Rushmi
o S and S - abmu
o Ix - Georgia
o Diagnoses - Me
o Mx - Jacqui
o Marrow transplant - sam
o ComplicationsDillys
o Prognosis - Kylie
o
Task
• What is massive splenomegaly? - Hasif
• Types of anaemia - Steph
o Hypo/normo, hypochromic
o Macro/norma/ chormic cytic
• Why some people can’t donate blood - lional
Friday, June 5, 2009
ECG etc.
ECG – Investigating PE
- Small/medium pulmonary embolism
· Usually normal, except for sinus tachycardia
· Sometimes atrial fibrillation another tachy-arrhythmia occurs
· May be evidence of right ventricular strain
- massive pulmonary emboli
· Show right atrial dilation with tall peaked P waves in lead II
· Right ventricular strain and dilation give rise to right axis deviation, some degree of right bundle branch block, and T wave inversion in the right precordial leads
- multiple recurrent pulmonary emboli
· Can be normal or show signs of pulmonary hypertension
- acute pulmonary embolism
· S wave in lead I
· A Q wave in lead III
· An inverted T wave in lead III
· Sinus tachycardia
· Incomplete right bundle branch block pattern (R wave in aVR and V1 and an S wave in V6)
P Wave
- An impulse that begins in the SA node is not recorded on the ECG, however –
- The spread of depolarisation through the atria (atrial depolarisation) is observed
- First phase of P wave – electrical stimulation from the SA node stimulates the right atrium and reaches the AV node
- Downslope of P wave – stimulation of the left atrium
- Atria begin to repolarise at the same time the ventricles depolarise
- Wave of atrial repolarisation is lost in the QRS complex
- Normal Characteristics of a P Wave
o Smooth and rounded
o No more than 2.5mm in height
o No more than 0.11 sec in duration
o Positive in leads I, II, aVF and V2-V6
QRS Complex
- Spread of electrical impulse through the ventricles (ventricular depolarisation)
- Depolarisation = contraction, thus, ventricles contract shortly after QRS complex begins
- Much larger as there is a considerably larger muscle mass being depolarised
- QRS duration – measurement of the time required for ventricular depolarisation
- Adult – normal duration – 0.06 – 0.10 seconds
- If conduction is delayed, QRS complex produced by the ventricle is wider
- Normal characteristics of the QRS complex
- Normal duration of the QRS complex in an adult varies between 0.06 and 0.10 sec
- A normal Q wave is less than 0.04 sec in duration and less than 1/3 the amplitude of the R wave in that lead
T Wave
- Ventricular repolarisation
- Slightly asymmetric – peak is slightly closer to the end than the beginning
- Normal characteristics of T wave
- Slightly asymmetric
- T waves are not normally more than 5mm in height in any limb lead or 10mm in any chest lead; T waves are not normally less than 0.5mm in height in leads I and II
U Wave
- Not always seen, cause not known
- Normal characteristics
- Rounded and symmetric
- Usually less than 1.5mm in height and smaller than in the preceding T wave
- In general, a U wave more than 1.5mm in height in any lead is considered abnormal
Segments
PR Segment
- Horizontal line between the end of the P wave and the start of the QRS complex
- Activation of the AV node, the bundle of His, the bundle branches and the Purkinje fibres
ST segment
- ST segment is between the QRS complex and the T wave
- Early part of repolarisation of the right and left ventricles
- ST segment deviation
- Myocardial Ischaemia
- Injury
- Infarction
- Normal characteristics of an ST segment
- Begins with the QRS complex and ends with the onset of the T wave
- In the limb leads, the normal ST segment is isoelectric (flat) but may normally be slightly elevated or depressed
- In the chest leads, ST segment deviation may vary from -0.5 to +2mm
TP Segment
- Between T wave and P wave
- Isoelectric when the heart rate is within normal limits
- With rapid heart rates, the TP segment is often unrecognisable because the P wave encroaches the preceding T wave
Intervals
An interval is a waveform and a segment
PR Intervals
- P wave + PR segment = PR interval
- PRI changes with HR but normally measures 0.12 to 0.20 sec in adults
- As HR increases, the duration of the PR interval shortens
- A conduction problem above the level of the bundle branches will largely affect the P wave and PR interval
- Normal characteristics of the PR interval
- Normally measures 0.12 to 0.20 sec in adults; may be shorter in children and longer in old people
- Normally shortens as heart rate increases
QT Interval
- This represents total ventricular activity à the time from ventricular depolarisation (activation) to repolarisation (recovery)
- Start of QRS Complex + End of T Wave = QT Interval
- Varies according to age, gender and heart rate
Analysing a Rhythm Strip
Assess the rate
- 6 Second Method
o To determine ventricular rate
o Count the number of QRS Complexes within a 6 second period
o Multiply this by 10 to find the number of complexes in a minute
o Can be used for regular and irregular rhythms
- Large Boxes
o To determine ventricular rate
o Count number of large boxes between two consecutive R waves (R-R interval)
o Divide this number into 300
o To determine atrial rate
o Count number of large boxes between two consecutive P waves (P-P interval)
o Divide this number into 300
Assess rhythm
- Rhythm indicates the site of origin of an electrical impulse (eg sinus rhythm, junctional rhythm)
- Also used to describe the regularity or irregularity of waveforms
- We assess regularity by measuring the distance between the QRS waves
Identify and examine P waves
- To locate P waves, look to the left of the QRS complex
- Normally, P waves looking similar in size, shape and position
- If no P wave is present, the rhythm originated in the AV junction or the ventricles
- If one P wave is present before each QRS and the QRS is narrow:
o Is the P wave positive? If so, the rhythm probably began in the SA node
o Is the P wave negative or absent? If so, and the QRS complexes occur regularly, the rhythm probably started in the AV junction
Assess Intervals (Evaluate Conduction)
PR Interval
- Measured from where the P waves leaves the baseline to the beginning of the QRS Complex
- Normal – 0.12 to 0.20 seconds
- If they are the same – ‘constant’
- ‘lengthening’ – dysrhythmia
QRS Duration
- Narrow (normal) if less than 0.10 seconds
- Wide – more than 0.10 seconds
QT Interval
- Measure the QT interval in the leads that show the largest amplitude T waves
- Measured from beginning of QRS complex to end of T wave
- Duration varies according to age, gender and heart rate
R-R and P-P Intervals
To determine the rate and regularity of a cardiac rhythm, the intervals are used
o R-R interval – measure and compare distance – ventricular rhythm
o P-P – atrial rhythm
· T wave
o Negative – MI
o Tall, pointed – hyperkalemia
- Small/medium pulmonary embolism
· Usually normal, except for sinus tachycardia
· Sometimes atrial fibrillation another tachy-arrhythmia occurs
· May be evidence of right ventricular strain
- massive pulmonary emboli
· Show right atrial dilation with tall peaked P waves in lead II
· Right ventricular strain and dilation give rise to right axis deviation, some degree of right bundle branch block, and T wave inversion in the right precordial leads
- multiple recurrent pulmonary emboli
· Can be normal or show signs of pulmonary hypertension
- acute pulmonary embolism
· S wave in lead I
· A Q wave in lead III
· An inverted T wave in lead III
· Sinus tachycardia
· Incomplete right bundle branch block pattern (R wave in aVR and V1 and an S wave in V6)
P Wave
- An impulse that begins in the SA node is not recorded on the ECG, however –
- The spread of depolarisation through the atria (atrial depolarisation) is observed
- First phase of P wave – electrical stimulation from the SA node stimulates the right atrium and reaches the AV node
- Downslope of P wave – stimulation of the left atrium
- Atria begin to repolarise at the same time the ventricles depolarise
- Wave of atrial repolarisation is lost in the QRS complex
- Normal Characteristics of a P Wave
o Smooth and rounded
o No more than 2.5mm in height
o No more than 0.11 sec in duration
o Positive in leads I, II, aVF and V2-V6
QRS Complex
- Spread of electrical impulse through the ventricles (ventricular depolarisation)
- Depolarisation = contraction, thus, ventricles contract shortly after QRS complex begins
- Much larger as there is a considerably larger muscle mass being depolarised
- QRS duration – measurement of the time required for ventricular depolarisation
- Adult – normal duration – 0.06 – 0.10 seconds
- If conduction is delayed, QRS complex produced by the ventricle is wider
- Normal characteristics of the QRS complex
- Normal duration of the QRS complex in an adult varies between 0.06 and 0.10 sec
- A normal Q wave is less than 0.04 sec in duration and less than 1/3 the amplitude of the R wave in that lead
T Wave
- Ventricular repolarisation
- Slightly asymmetric – peak is slightly closer to the end than the beginning
- Normal characteristics of T wave
- Slightly asymmetric
- T waves are not normally more than 5mm in height in any limb lead or 10mm in any chest lead; T waves are not normally less than 0.5mm in height in leads I and II
U Wave
- Not always seen, cause not known
- Normal characteristics
- Rounded and symmetric
- Usually less than 1.5mm in height and smaller than in the preceding T wave
- In general, a U wave more than 1.5mm in height in any lead is considered abnormal
Segments
PR Segment
- Horizontal line between the end of the P wave and the start of the QRS complex
- Activation of the AV node, the bundle of His, the bundle branches and the Purkinje fibres
ST segment
- ST segment is between the QRS complex and the T wave
- Early part of repolarisation of the right and left ventricles
- ST segment deviation
- Myocardial Ischaemia
- Injury
- Infarction
- Normal characteristics of an ST segment
- Begins with the QRS complex and ends with the onset of the T wave
- In the limb leads, the normal ST segment is isoelectric (flat) but may normally be slightly elevated or depressed
- In the chest leads, ST segment deviation may vary from -0.5 to +2mm
TP Segment
- Between T wave and P wave
- Isoelectric when the heart rate is within normal limits
- With rapid heart rates, the TP segment is often unrecognisable because the P wave encroaches the preceding T wave
Intervals
An interval is a waveform and a segment
PR Intervals
- P wave + PR segment = PR interval
- PRI changes with HR but normally measures 0.12 to 0.20 sec in adults
- As HR increases, the duration of the PR interval shortens
- A conduction problem above the level of the bundle branches will largely affect the P wave and PR interval
- Normal characteristics of the PR interval
- Normally measures 0.12 to 0.20 sec in adults; may be shorter in children and longer in old people
- Normally shortens as heart rate increases
QT Interval
- This represents total ventricular activity à the time from ventricular depolarisation (activation) to repolarisation (recovery)
- Start of QRS Complex + End of T Wave = QT Interval
- Varies according to age, gender and heart rate
Analysing a Rhythm Strip
Assess the rate
- 6 Second Method
o To determine ventricular rate
o Count the number of QRS Complexes within a 6 second period
o Multiply this by 10 to find the number of complexes in a minute
o Can be used for regular and irregular rhythms
- Large Boxes
o To determine ventricular rate
o Count number of large boxes between two consecutive R waves (R-R interval)
o Divide this number into 300
o To determine atrial rate
o Count number of large boxes between two consecutive P waves (P-P interval)
o Divide this number into 300
Assess rhythm
- Rhythm indicates the site of origin of an electrical impulse (eg sinus rhythm, junctional rhythm)
- Also used to describe the regularity or irregularity of waveforms
- We assess regularity by measuring the distance between the QRS waves
Identify and examine P waves
- To locate P waves, look to the left of the QRS complex
- Normally, P waves looking similar in size, shape and position
- If no P wave is present, the rhythm originated in the AV junction or the ventricles
- If one P wave is present before each QRS and the QRS is narrow:
o Is the P wave positive? If so, the rhythm probably began in the SA node
o Is the P wave negative or absent? If so, and the QRS complexes occur regularly, the rhythm probably started in the AV junction
Assess Intervals (Evaluate Conduction)
PR Interval
- Measured from where the P waves leaves the baseline to the beginning of the QRS Complex
- Normal – 0.12 to 0.20 seconds
- If they are the same – ‘constant’
- ‘lengthening’ – dysrhythmia
QRS Duration
- Narrow (normal) if less than 0.10 seconds
- Wide – more than 0.10 seconds
QT Interval
- Measure the QT interval in the leads that show the largest amplitude T waves
- Measured from beginning of QRS complex to end of T wave
- Duration varies according to age, gender and heart rate
R-R and P-P Intervals
To determine the rate and regularity of a cardiac rhythm, the intervals are used
o R-R interval – measure and compare distance – ventricular rhythm
o P-P – atrial rhythm
· T wave
o Negative – MI
o Tall, pointed – hyperkalemia
Investigations & Prognosis
DVT Investigations
1) ultrasound (doppler) - transducer is placed over leg and send sound waves through the tissue, reflect back and waves is shown as a moving image on the screen. clot maybe visible. series done over a few days to see if the clot is growing or new one is developing
2) CT/MRI scans. computerized tomography (CT) and magnetic resonance imaging(MRI) - visual images of veins and show clot present. usually for pregnant ladies & renal problem people with dye-related problems.
3) blood test - elevated level of D-dimer (clot-dissolving substance). however, D-dimer is elevated in other things too. used for RULING OUT dvt or identifying those at risk of recurrence. look for inherited defects in clotting system as well.
4) venography - dye injected into large vein @ foot/ankle. x-ray creates image of veins to look for clots. abit invasive, so not less used.
DVT Prognosis
1) PE! 3% fatal!
2) 15% people get postphlebitic syndrome(post-thrombotic synd) - syndrome used to describe a collection of signs & symptoms
(a) oedema in legs (usually medial lower leg)
(b) pain
(c) skin discolaration
(d) dermatitis
(e) venous claudication
(f) nocturnal cramping
(g) ulceration
due to damage of veins from blood clot. this reduces blood flow to damaged areas. can occur a few years after DVT. (Rx: aspirin, diuretics, compression stockings)
PE Investigations
1) CXR - cannot diagnose PE but can rule out other conditions
2) V/Q scan - use small amts of radioisoptopes (SMALL AMT!) attached to radiopharmaceuticals which is inhaled to take pictures of movement of air in lungs. different radiopharm is injected into vein in arm & pictures of blood flow in blood vessels of lungs are taken. results are compared. normal lung scan can rule out PE but not DVT. thus not used much now.
*3) Spiral (helical) CT scan
CT: 2-d slices seen of organ by thin x-ray beams passing through organs. dye is used to visualize.
spiral CT: scanner rotates continously around body, to create 3-d images! faster - scan pulm arteries in <20secs. however, exposes to slightly more radiation then standard x-ray + allergic reaction to contrast medium.
4) Pulmonary angiogram - blood flow in lung arteries. most accurate diagnosis but requires high degree of skills & risks. usually performed when other tests fail to give Dx. catheter is inserted into femoral vein to pulm arteries. dye is injected and x-ray is taken.
risk: change in heart rhythm. dye may cause kidney damage with ppl with decrease renal function (usually temp). developing a hematoma at puncture site.
PE Prognosis
1) 1/3 undiagnosed - fatal
2) once had, increase recurrence risk
3) pulmonary HPT - large number of clots obstruct blood flow in lung blood vessles for long time causing right heart to be overworked
4) cor pulmonale - right ventricle enlarged & fails.
1) ultrasound (doppler) - transducer is placed over leg and send sound waves through the tissue, reflect back and waves is shown as a moving image on the screen. clot maybe visible. series done over a few days to see if the clot is growing or new one is developing
2) CT/MRI scans. computerized tomography (CT) and magnetic resonance imaging(MRI) - visual images of veins and show clot present. usually for pregnant ladies & renal problem people with dye-related problems.
3) blood test - elevated level of D-dimer (clot-dissolving substance). however, D-dimer is elevated in other things too. used for RULING OUT dvt or identifying those at risk of recurrence. look for inherited defects in clotting system as well.
4) venography - dye injected into large vein @ foot/ankle. x-ray creates image of veins to look for clots. abit invasive, so not less used.
DVT Prognosis
1) PE! 3% fatal!
2) 15% people get postphlebitic syndrome(post-thrombotic synd) - syndrome used to describe a collection of signs & symptoms
(a) oedema in legs (usually medial lower leg)
(b) pain
(c) skin discolaration
(d) dermatitis
(e) venous claudication
(f) nocturnal cramping
(g) ulceration
due to damage of veins from blood clot. this reduces blood flow to damaged areas. can occur a few years after DVT. (Rx: aspirin, diuretics, compression stockings)
PE Investigations
1) CXR - cannot diagnose PE but can rule out other conditions
2) V/Q scan - use small amts of radioisoptopes (SMALL AMT!) attached to radiopharmaceuticals which is inhaled to take pictures of movement of air in lungs. different radiopharm is injected into vein in arm & pictures of blood flow in blood vessels of lungs are taken. results are compared. normal lung scan can rule out PE but not DVT. thus not used much now.
*3) Spiral (helical) CT scan
CT: 2-d slices seen of organ by thin x-ray beams passing through organs. dye is used to visualize.
spiral CT: scanner rotates continously around body, to create 3-d images! faster - scan pulm arteries in <20secs. however, exposes to slightly more radiation then standard x-ray + allergic reaction to contrast medium.
4) Pulmonary angiogram - blood flow in lung arteries. most accurate diagnosis but requires high degree of skills & risks. usually performed when other tests fail to give Dx. catheter is inserted into femoral vein to pulm arteries. dye is injected and x-ray is taken.
risk: change in heart rhythm. dye may cause kidney damage with ppl with decrease renal function (usually temp). developing a hematoma at puncture site.
PE Prognosis
1) 1/3 undiagnosed - fatal
2) once had, increase recurrence risk
3) pulmonary HPT - large number of clots obstruct blood flow in lung blood vessles for long time causing right heart to be overworked
4) cor pulmonale - right ventricle enlarged & fails.
Thursday, June 4, 2009
Full Blood Examination + INR, APTT D-Dimer
Haemoglobin (Hb)
Haemoglobin is an iron-containing compound found in the red blood cells, which transports oxygen around the body. Measuring the concentration of haemoglobin in the blood can help diagnose anaemia, a condition caused by a deficiency of haemoglobin. Anaemia can arise due to:
too few red blood cells;
inadequate iron intake;
inadequate folate or vitamin B12 intake;
microscopic bleeding or other blood loss;
blood cell destruction;
a chronic illness; or
a defect in the haemoglobin molecule itself.
This measurement may also detect abnormally high concentrations of haemoglobin. This may occur in people with chronic lung disease, as an adaptation to high altitudes, or because of an abnormal increase in red cell production by the bone marrow (polycythaemia vera).
The normal haemoglobin level for adult males is 130-170 g/L, and 120-150 g/L for adult females.
Red cell count (RCC)
Red cell count is an estimation of the number of red blood cells per litre of blood.
Abnormally low numbers of red blood cells may indicate anaemia as a result of blood loss, bone marrow failure, malnutrition such as iron deficiency, over-hydration, or mechanical damage to red blood cells.
Abnormally high numbers of red blood cells may indicate congenital heart disease, some lung diseases, dehydration, kidney disease or polycythaemia vera.
The normal red cell count for adult males is 4.5-5.5 x 1012/L, and 3.8-4.8 x 1012/L for adult females.
Packed cell volume (PCV) or haematocrit (Hct)
Haematocrit is a measure of the percentage of red blood cells to the total blood volume.
A low haematocrit may indicate anaemia, blood loss, bone marrow failure, leukaemia, multiple myeloma, nutritional deficiency, over-hydration or rheumatoid arthritis.
A high haematocrit may indicate dehydration (for example, due to burns or diarrhoea), eclampsia (a serious condition that can occur during pregnancy) or polycythaemia vera.
The normal haematocrit range for adult males is 40-50 per cent, and 36-46 per cent for adult females.
Mean cell volume or mean corpuscular volume (MCV)
Mean cell volume is an estimate of the volume of red blood cells. It is useful for determining the type of anaemia a person might have.
A low MCV may indicate iron deficiency, chronic disease, pregnancy, anaemia due to blood cell destruction or bone marrow disorders.
A high MCV may indicate anaemia due to nutritional deficiencies, bone marrow abnormalities, liver disease, alcoholism, chronic lung disease, or therapy with certain medications.
The normal MCV range for adults is 83-101 fL.
Mean cell haemoglobin (MCH) and mean cell haemoglobin concentration (MCHC)
These measures, also known as mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration, are further guides to the investigation of anaemia.
The MCH is the haemoglobin content of the average red cell. The MCHC is the average haemoglobin concentration in a given volume of packed red cells.
The MCH may be low in types of anaemia where the red blood cells are abnormally small, or high in other types of anaemia where the red blood cells are enlarged (for example, as a result of folic acid or vitamin B12 deficiency).
The MCHC is low in iron deficiency, blood loss, pregnancy and anaemias caused by chronic disease.
The normal MCH range for adults is 27-32 pg, and the normal MCHC range is 315-345 g/L.
White cell (leucocyte) count
White cell count estimates the total number of white blood cells per litre of blood.
An abnormal high or low white cell count can indicate many possible medical conditions and a leucocyte differential count, which provides numbers of the different types of white cells, is usually needed to help make any diagnosis.
Abnormally low numbers of white blood cells may indicate liver or spleen disorders, bone marrow disorders, or exposure to radiation or toxic substances.
Abnormally high levels of white blood cells may indicate infection, tissue damage, leukaemia, or inflammatory diseases.
The normal white cell count for adults is 4.0-10.0 x 109/L.
Leucocyte (white cell) differential count
Leucocyte differential count provides an estimate of the numbers of the 5 main types of white blood cells. These are: neutrophils; monocytes; lymphocytes; eosinophils; and basophils.
Each of the 5 types has a specific role in the body.
Neutrophils and monocytes protect the body against bacteria and eat up small particles of foreign matter.
Lymphocytes are involved in the immune process, producing antibodies against foreign organisms, protecting against viruses and fighting cancer.
Eosinophils kill parasites and are involved in allergic responses. High numbers of eosinophils may be associated with worm infections or exposure to substances that cause allergic reactions.
Basophils also take part in allergic responses and increased basophil production may be associated with bone marrow disorders or viral infection.
The normal ranges for the number of the different types of white cells in adults are:
Neutrophils: 2.0-7.0 x 109/L
Eosinophils: 0.02-0.5 x 109/L
Basophils: 0.05-0.1 x 109/L
Monocytes: 0.2-1.0 x 109/L
Lymphocytes: 1.0-3.0 x 109/L
Platelet count
Platelet count is an estimation of the number of platelets per litre of blood. Abnormally low numbers of platelets is known as thrombocytopenia, while an abnormally high level of platelets is known as thrombocytosis.
Platelet counts are often used to monitor medications such as heparin, which may cause low numbers of platelets, as well as medications that can have toxic effects on bone marrow. They may also be used to help diagnose problems associated with abnormal bleeding or bruising.
The normal platelet count for adults is 150-400 x 109/L.
The prothrombin time (PT) and its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) are measures of the extrinsic pathway of coagulation. They are used to determine the clotting tendency of blood, in the measure of warfarin dosage, liver damage, and vitamin K status. The reference range for prothrombin time is usually around 12–15 seconds; the normal range for the INR is 0.8–1.2. PT measures factors II, V, VII, X and fibrinogen. It is used in conjunction with the activated partial thromboplastin time (aPTT) which measures the intrinsic pathway.
The prothrombin time is the time it takes plasma to clot after addition of tissue factor (obtained from animals). This measures the quality of the extrinsic pathway (as well as the common pathway) of coagulation.
The speed of the extrinsic pathway is greatly affected by levels of factor VII in the body. Factor VII has a short half-life and its synthesis requires vitamin K. The prothrombin time can be prolonged as a result of deficiencies in vitamin K, which can be caused by warfarin, malabsorption, or lack of intestinal colonization by bacteria (such as in newborns). In addition, poor factor VII synthesis (due to liver disease) or increased consumption (in disseminated intravascular coagulation) may prolong the PT.
A high INR level such as INR=5 indicates that there is a high chance of bleeding, whereas if the INR=0.5 then there is a high chance of having a clot. Normal range for a healthy person is 0.9–1.3, and for people on warfarin therapy, 2.0–3.0, although the target INR may be higher in particular situations, such as for those with a mechanical heart valve, or bridging warfarin with a low-molecular weight heparin (such as enoxaparin) perioperatively.
APTT - A phlebotomist collects blood samples in vacu-tubes with oxalate or citrate to arrest coagulation by binding calcium. The specimen is then delivered to the laboratory. In order to activate the intrinsic pathway, phospholipid, an activator (such as silica, celite, kaolin, ellagic acid), and calcium (to reverse the anticoagulant effect of the oxalate) are mixed into the plasma sample . The time is measured until a thrombus (clot) forms. This testing is performed by a medical technologist.
A positive D-dimer indicates the presence of an abnormally high level of fibrin degradation products in your body. It tells your doctor that there has been significant clot (thrombus) formation and breakdown in the body, but it does not tell the location or cause.
Haemoglobin is an iron-containing compound found in the red blood cells, which transports oxygen around the body. Measuring the concentration of haemoglobin in the blood can help diagnose anaemia, a condition caused by a deficiency of haemoglobin. Anaemia can arise due to:
too few red blood cells;
inadequate iron intake;
inadequate folate or vitamin B12 intake;
microscopic bleeding or other blood loss;
blood cell destruction;
a chronic illness; or
a defect in the haemoglobin molecule itself.
This measurement may also detect abnormally high concentrations of haemoglobin. This may occur in people with chronic lung disease, as an adaptation to high altitudes, or because of an abnormal increase in red cell production by the bone marrow (polycythaemia vera).
The normal haemoglobin level for adult males is 130-170 g/L, and 120-150 g/L for adult females.
Red cell count (RCC)
Red cell count is an estimation of the number of red blood cells per litre of blood.
Abnormally low numbers of red blood cells may indicate anaemia as a result of blood loss, bone marrow failure, malnutrition such as iron deficiency, over-hydration, or mechanical damage to red blood cells.
Abnormally high numbers of red blood cells may indicate congenital heart disease, some lung diseases, dehydration, kidney disease or polycythaemia vera.
The normal red cell count for adult males is 4.5-5.5 x 1012/L, and 3.8-4.8 x 1012/L for adult females.
Packed cell volume (PCV) or haematocrit (Hct)
Haematocrit is a measure of the percentage of red blood cells to the total blood volume.
A low haematocrit may indicate anaemia, blood loss, bone marrow failure, leukaemia, multiple myeloma, nutritional deficiency, over-hydration or rheumatoid arthritis.
A high haematocrit may indicate dehydration (for example, due to burns or diarrhoea), eclampsia (a serious condition that can occur during pregnancy) or polycythaemia vera.
The normal haematocrit range for adult males is 40-50 per cent, and 36-46 per cent for adult females.
Mean cell volume or mean corpuscular volume (MCV)
Mean cell volume is an estimate of the volume of red blood cells. It is useful for determining the type of anaemia a person might have.
A low MCV may indicate iron deficiency, chronic disease, pregnancy, anaemia due to blood cell destruction or bone marrow disorders.
A high MCV may indicate anaemia due to nutritional deficiencies, bone marrow abnormalities, liver disease, alcoholism, chronic lung disease, or therapy with certain medications.
The normal MCV range for adults is 83-101 fL.
Mean cell haemoglobin (MCH) and mean cell haemoglobin concentration (MCHC)
These measures, also known as mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration, are further guides to the investigation of anaemia.
The MCH is the haemoglobin content of the average red cell. The MCHC is the average haemoglobin concentration in a given volume of packed red cells.
The MCH may be low in types of anaemia where the red blood cells are abnormally small, or high in other types of anaemia where the red blood cells are enlarged (for example, as a result of folic acid or vitamin B12 deficiency).
The MCHC is low in iron deficiency, blood loss, pregnancy and anaemias caused by chronic disease.
The normal MCH range for adults is 27-32 pg, and the normal MCHC range is 315-345 g/L.
White cell (leucocyte) count
White cell count estimates the total number of white blood cells per litre of blood.
An abnormal high or low white cell count can indicate many possible medical conditions and a leucocyte differential count, which provides numbers of the different types of white cells, is usually needed to help make any diagnosis.
Abnormally low numbers of white blood cells may indicate liver or spleen disorders, bone marrow disorders, or exposure to radiation or toxic substances.
Abnormally high levels of white blood cells may indicate infection, tissue damage, leukaemia, or inflammatory diseases.
The normal white cell count for adults is 4.0-10.0 x 109/L.
Leucocyte (white cell) differential count
Leucocyte differential count provides an estimate of the numbers of the 5 main types of white blood cells. These are: neutrophils; monocytes; lymphocytes; eosinophils; and basophils.
Each of the 5 types has a specific role in the body.
Neutrophils and monocytes protect the body against bacteria and eat up small particles of foreign matter.
Lymphocytes are involved in the immune process, producing antibodies against foreign organisms, protecting against viruses and fighting cancer.
Eosinophils kill parasites and are involved in allergic responses. High numbers of eosinophils may be associated with worm infections or exposure to substances that cause allergic reactions.
Basophils also take part in allergic responses and increased basophil production may be associated with bone marrow disorders or viral infection.
The normal ranges for the number of the different types of white cells in adults are:
Neutrophils: 2.0-7.0 x 109/L
Eosinophils: 0.02-0.5 x 109/L
Basophils: 0.05-0.1 x 109/L
Monocytes: 0.2-1.0 x 109/L
Lymphocytes: 1.0-3.0 x 109/L
Platelet count
Platelet count is an estimation of the number of platelets per litre of blood. Abnormally low numbers of platelets is known as thrombocytopenia, while an abnormally high level of platelets is known as thrombocytosis.
Platelet counts are often used to monitor medications such as heparin, which may cause low numbers of platelets, as well as medications that can have toxic effects on bone marrow. They may also be used to help diagnose problems associated with abnormal bleeding or bruising.
The normal platelet count for adults is 150-400 x 109/L.
The prothrombin time (PT) and its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) are measures of the extrinsic pathway of coagulation. They are used to determine the clotting tendency of blood, in the measure of warfarin dosage, liver damage, and vitamin K status. The reference range for prothrombin time is usually around 12–15 seconds; the normal range for the INR is 0.8–1.2. PT measures factors II, V, VII, X and fibrinogen. It is used in conjunction with the activated partial thromboplastin time (aPTT) which measures the intrinsic pathway.
The prothrombin time is the time it takes plasma to clot after addition of tissue factor (obtained from animals). This measures the quality of the extrinsic pathway (as well as the common pathway) of coagulation.
The speed of the extrinsic pathway is greatly affected by levels of factor VII in the body. Factor VII has a short half-life and its synthesis requires vitamin K. The prothrombin time can be prolonged as a result of deficiencies in vitamin K, which can be caused by warfarin, malabsorption, or lack of intestinal colonization by bacteria (such as in newborns). In addition, poor factor VII synthesis (due to liver disease) or increased consumption (in disseminated intravascular coagulation) may prolong the PT.
A high INR level such as INR=5 indicates that there is a high chance of bleeding, whereas if the INR=0.5 then there is a high chance of having a clot. Normal range for a healthy person is 0.9–1.3, and for people on warfarin therapy, 2.0–3.0, although the target INR may be higher in particular situations, such as for those with a mechanical heart valve, or bridging warfarin with a low-molecular weight heparin (such as enoxaparin) perioperatively.
APTT - A phlebotomist collects blood samples in vacu-tubes with oxalate or citrate to arrest coagulation by binding calcium. The specimen is then delivered to the laboratory. In order to activate the intrinsic pathway, phospholipid, an activator (such as silica, celite, kaolin, ellagic acid), and calcium (to reverse the anticoagulant effect of the oxalate) are mixed into the plasma sample . The time is measured until a thrombus (clot) forms. This testing is performed by a medical technologist.
A positive D-dimer indicates the presence of an abnormally high level of fibrin degradation products in your body. It tells your doctor that there has been significant clot (thrombus) formation and breakdown in the body, but it does not tell the location or cause.
Wednesday, June 3, 2009
Necrotising Fasciitis
Definition
Rare but very severe bacterial infection of deep fascia with secondary necrosis of soft tissue (e.g. muscle, skin).
Aetiology
Type I – Polymicrobial
· Mixed aerobic and anaerobic bacteria
Type II - Monomicrobial
· Group A Streptococcus (e.g. Streptococcus pyogenes)
· Staphylococcus aureus (commonly MRSA)
Pathogenesis
Trauma causing the breaking of skin (e.g. surgery, cut, scratch) allows bacteria to enter body. The bacteria colonises soft tissue and spreads in the fascial plane, releasing toxins which destroy the soft tissue. Certain toxins can cause systemic effects (e.g. renal failure, septic shock).
Signs and Symptoms
Symptoms start at site of infection – intense pain in excess of that expected with visual inspection. Signs of inflammation apparent – redness, swelling, heat. Spread of infection leads to a rapidly growing bronze- or purple-coloured patch. Within an hour, the skin may break open and exudation may occur.
Generalised signs and symptoms: malaise, fever, sweating, chills, nausea, dizziness, weakness, shock.
Without treatment, death can occur rapidly (73% untreated mortality rate).
Investigations
CT scan to view extent of necrosis.
Culture to confirm bacteria and determine antibiotic use.
Management
Before culture results, presumptive broad-spectrum aggressive intravenous antibiotic therapy. Intravenous donor antibodies. Targeted antibiotic therapy after identification of pathogenic bacteria.
Surgery to drain infected areas and debridement of necrotic tissue. Consider amputation if infection cannot be controlled. Skin grafting after infection cessation.
Hyperbaric oxygen therapy if bacteria is anaerobic.
Prognosis
Scarring and deformity common.
High death rate even with aggressive treatment.
Complications
Local progressive tissue damage, systemic infection (sepsis, shock), scarring and disfiguration, functional limb loss, death.
Prevention
Proper asepsis following penetrative trauma and surgical incisions.
Signs and Symptoms
DVT
Symptoms can vary with location and size of blood clot, but generally are:
- pain in the affected calf
- difficulty walking due to pain, or pain worsen when walking
Signs
• tenderness
• oedema
• sensation of warmth
• skins appear blue or red
• Engorged superficial veins
• Homan’s sign
PE
Again, symptoms depend on location and size of blood clot:
- shortness of breath
- palpitations
- chest pain, which may radiate to shoulder, arm, jaw or neck
- dizziness
- haemoptysis
Signs
• cyanosis
• tachypnoea
• tachycardia
• hypotension
• raised JVP
• pleural effusion
• pyrexia
Symptoms can vary with location and size of blood clot, but generally are:
- pain in the affected calf
- difficulty walking due to pain, or pain worsen when walking
Signs
• tenderness
• oedema
• sensation of warmth
• skins appear blue or red
• Engorged superficial veins
• Homan’s sign
PE
Again, symptoms depend on location and size of blood clot:
- shortness of breath
- palpitations
- chest pain, which may radiate to shoulder, arm, jaw or neck
- dizziness
- haemoptysis
Signs
• cyanosis
• tachypnoea
• tachycardia
• hypotension
• raised JVP
• pleural effusion
• pyrexia
Treatment/management DVT
The aims of treatment are to relieve symptoms, reduce the risk of PE or paradoxical embolism to the systemic circulation, prevent post-thrombotic syndrome, and prevent recurrence.
Initial anticoagulation
Anticoagulation is the mainstay of treatment for DVT.
Initial treatment of DVT is heparin, as it is convenient to use and has a favorable side-effects profile. It can be used once or twice daily
LMWH (low molecular weight heparin) has a predictable anticoagulant response, so it can be given in a fixed weight-adjusted subcutaneous dose without laboratory monitoring in most patients. This allows out-of-hospital treatment in more than 80% of patients with acute DVT.
UFH (unfractionated heparin) is the treatment of choice in patients at high risk of bleeding or undergoing invasive procedures, and in patients with renal failure because of its shorter half-life, reversibility with protamine sulfate, and extra-renal metabolism.
In most cases, warfarin can be started on the first day. LMWH or UFH should be continued for at least 5 days and until the international normalised ratio (INR) has exceeded 2.0 on at least two occasions, 24 hours apart. Major bleeding occurs in 1%–5% of patients during initial treatment.
In patients with extensive ilio-femoral DVT and circulatory compromise, LMWH or UFH should be continued for at least 7 days, and initiation of warfarin should be delayed until anticoagulation has been therapeutic for several days.
Long-term anticoagulation
Warfarin (target INR, 2.0–3.0) is the anticoagulant of choice for long-term treatment of most patients with DVT, because it can be given orally and is highly effective, reducing the risk of recurrent VTE by 80%–90% during treatment.
In patients with provoked DVT, the risk of recurrent VTE after discontinuation of warfarin is 1%–4% per year. Generally, warfarin treatment should be continued for 3 months, although there is some evidence that 6 weeks treatment is as effective as 3 months in patients with provoked distal DVT.
In patients with unprovoked DVT, major chronic predispositions, or active malignancy, the risk of recurrent VTE after discontinuation of warfarin is substantially higher (at least 5%–10% per year) than for provoked events (≤ 4% per year). Decisions regarding the duration of anticoagulant treatment should be individualised by balancing the absolute risk of recurrent VTE with the potential absolute benefits (80%–90% relative risk reduction) and cumulative risks of bleeding associated with anticoagulation.
Thrombolytic therapy and surgical embolectomy
Compared with heparin, thrombolysis improves vein patency and reduces the risk of post-thrombotic syndrome, but increases the risk of bleeding, and there is no evidence of a net clinical benefit. Thrombolysis and surgical embolectomy have been used as limb-saving therapy in patients with extensive proximal DVT and circulatory compromise or venous gangrene.
Vena cava filter
Inferior vena cava filters are indicated to prevent pulmonary embolism in patients with DVT who are ineligible for anticoagulant therapy or who experience embolism despite adequate anticoagulation. Filters do not obviate the need for anticoagulation because they are associated with an increased risk of recurrent DVT. However, the optimal duration of anticoagulation in patients with vena cava filters in whom anticoagulation is deemed safe is uncertain.
Graduated compression stockings
Graduated compression stockings reduce the risk of post-thrombotic syndrome and should be used in the absence of contra-indications (eg, pre-existing leg ulceration or extensive varicosities).
And PE
Acute high-flow oxygen unless significant COPD, bed rest and analgesia. Severe cases IV fluids and ionotropic agents to improve right heart, very ill require ICU.
Prevention of furtheur emboli
• IV heparin, initial large bolus then continue infusion at a lower rate.
• LMWH, UFH have shown no difference in prevention of further emboli
• Oral anticoagulants begun after 48 hours, continue for 6 weeks – 6 months. Heparin is tapered off. Can be continued lifelong.
Dissolution of the thrombus
• Fibrinolytic therapy e.g. streptokinase following major embolism. Hourly up to 12- 72 hours.
• Surgical embolectomy is rarely necessary
Contraindications for anticoagulation and risk factors for anticoagulation-associated haemorrhage
Absolute contraindications
Active bleeding
Relative contraindications
Recent bleeding
Gastrointestinal bleeding within 2 weeks (eg, bleeding peptic ulcer)
Intracranial bleeding within 3 months
Recent major trauma
Bleeding diathesis
Coagulation defect
Severe thrombocytopenia (< 50 × 109/L); inherited or acquired platelet function defect
Uncontrolled hypertension
Endocarditis
Risk factors for anticoagulation-associated haemorrhage
Increasing age
Alcoholism
Cognitive impairment
Chronic corticosteroid use
Liver disease
Peptic ulcer disease
Polymorphisms for the gene encoding the hepatic microsomal enzyme CYP2CP and mutations of Ala-10 in the factor IX propeptide
References
• http://www.mja.com.au/public/issues/182_09_020505/ho10889_fm.html#elementId-1089801
• Kumar and Clarke 5th edition pg, 807 and 832
Sarah
The aims of treatment are to relieve symptoms, reduce the risk of PE or paradoxical embolism to the systemic circulation, prevent post-thrombotic syndrome, and prevent recurrence.
Initial anticoagulation
Anticoagulation is the mainstay of treatment for DVT.
Initial treatment of DVT is heparin, as it is convenient to use and has a favorable side-effects profile. It can be used once or twice daily
LMWH (low molecular weight heparin) has a predictable anticoagulant response, so it can be given in a fixed weight-adjusted subcutaneous dose without laboratory monitoring in most patients. This allows out-of-hospital treatment in more than 80% of patients with acute DVT.
UFH (unfractionated heparin) is the treatment of choice in patients at high risk of bleeding or undergoing invasive procedures, and in patients with renal failure because of its shorter half-life, reversibility with protamine sulfate, and extra-renal metabolism.
In most cases, warfarin can be started on the first day. LMWH or UFH should be continued for at least 5 days and until the international normalised ratio (INR) has exceeded 2.0 on at least two occasions, 24 hours apart. Major bleeding occurs in 1%–5% of patients during initial treatment.
In patients with extensive ilio-femoral DVT and circulatory compromise, LMWH or UFH should be continued for at least 7 days, and initiation of warfarin should be delayed until anticoagulation has been therapeutic for several days.
Long-term anticoagulation
Warfarin (target INR, 2.0–3.0) is the anticoagulant of choice for long-term treatment of most patients with DVT, because it can be given orally and is highly effective, reducing the risk of recurrent VTE by 80%–90% during treatment.
In patients with provoked DVT, the risk of recurrent VTE after discontinuation of warfarin is 1%–4% per year. Generally, warfarin treatment should be continued for 3 months, although there is some evidence that 6 weeks treatment is as effective as 3 months in patients with provoked distal DVT.
In patients with unprovoked DVT, major chronic predispositions, or active malignancy, the risk of recurrent VTE after discontinuation of warfarin is substantially higher (at least 5%–10% per year) than for provoked events (≤ 4% per year). Decisions regarding the duration of anticoagulant treatment should be individualised by balancing the absolute risk of recurrent VTE with the potential absolute benefits (80%–90% relative risk reduction) and cumulative risks of bleeding associated with anticoagulation.
Thrombolytic therapy and surgical embolectomy
Compared with heparin, thrombolysis improves vein patency and reduces the risk of post-thrombotic syndrome, but increases the risk of bleeding, and there is no evidence of a net clinical benefit. Thrombolysis and surgical embolectomy have been used as limb-saving therapy in patients with extensive proximal DVT and circulatory compromise or venous gangrene.
Vena cava filter
Inferior vena cava filters are indicated to prevent pulmonary embolism in patients with DVT who are ineligible for anticoagulant therapy or who experience embolism despite adequate anticoagulation. Filters do not obviate the need for anticoagulation because they are associated with an increased risk of recurrent DVT. However, the optimal duration of anticoagulation in patients with vena cava filters in whom anticoagulation is deemed safe is uncertain.
Graduated compression stockings
Graduated compression stockings reduce the risk of post-thrombotic syndrome and should be used in the absence of contra-indications (eg, pre-existing leg ulceration or extensive varicosities).
And PE
Acute high-flow oxygen unless significant COPD, bed rest and analgesia. Severe cases IV fluids and ionotropic agents to improve right heart, very ill require ICU.
Prevention of furtheur emboli
• IV heparin, initial large bolus then continue infusion at a lower rate.
• LMWH, UFH have shown no difference in prevention of further emboli
• Oral anticoagulants begun after 48 hours, continue for 6 weeks – 6 months. Heparin is tapered off. Can be continued lifelong.
Dissolution of the thrombus
• Fibrinolytic therapy e.g. streptokinase following major embolism. Hourly up to 12- 72 hours.
• Surgical embolectomy is rarely necessary
Contraindications for anticoagulation and risk factors for anticoagulation-associated haemorrhage
Absolute contraindications
Active bleeding
Relative contraindications
Recent bleeding
Gastrointestinal bleeding within 2 weeks (eg, bleeding peptic ulcer)
Intracranial bleeding within 3 months
Recent major trauma
Bleeding diathesis
Coagulation defect
Severe thrombocytopenia (< 50 × 109/L); inherited or acquired platelet function defect
Uncontrolled hypertension
Endocarditis
Risk factors for anticoagulation-associated haemorrhage
Increasing age
Alcoholism
Cognitive impairment
Chronic corticosteroid use
Liver disease
Peptic ulcer disease
Polymorphisms for the gene encoding the hepatic microsomal enzyme CYP2CP and mutations of Ala-10 in the factor IX propeptide
References
• http://www.mja.com.au/public/issues/182_09_020505/ho10889_fm.html#elementId-1089801
• Kumar and Clarke 5th edition pg, 807 and 832
Sarah
Subscribe to:
Posts (Atom)