Primary Thrombophilia - Clinicals, Diagnosis, and Management

Hematology

Clinicals - History

Fact Explanation
Introduction Primary Thrombophilia is inherited disorders of the haemostatic mechanism leading to thrombi formation (hypercoagulability state). This is commonly affects the venous system ( eg; Deep vein thrombosis, pulmonary embolism). Commonly seen in young population and precautions need to be taken in surgery, pregnancy and prolonged immobilization. Causes of inherited thrombophilia are activated protein c recistance, prothrombin gene mutation, protein C and protein S deficiency and antithrombin deficiency. Introduction
Primary Thrombophilia is inherited disorders of the haemostatic mechanism leading to thrombi formation (hypercoagulability state). This is commonly affects the venous system ( eg; Deep vein thrombosis, pulmonary embolism). Commonly seen in young population and precautions need to be taken in surgery, pregnancy and prolonged immobilization. Causes of inherited thrombophilia are activated protein c recistance, prothrombin gene mutation, protein C and protein S deficiency and antithrombin deficiency.
symptoms suggestive of deep vein thrombosis Patient will develop sudden onset severe limb pain with difficulty in moving. limb will be red and swollen. commonly affect lower limbs. symptoms suggestive of deep vein thrombosis
Patient will develop sudden onset severe limb pain with difficulty in moving. limb will be red and swollen. commonly affect lower limbs.
symptoms suggestive of pulmonary embolism Patient will develop sudden onset shortness of breath, cough, wheezing and haemoptysis following pulmonary embolization. symptoms suggestive of pulmonary embolism
Patient will develop sudden onset shortness of breath, cough, wheezing and haemoptysis following pulmonary embolization.
Symptoms suggestive of other venous thrombosis Though these presentations are uncommon patients can develop thrombus in other venous systems.
eg;
Cerebral venous thrombosis patient will be confused, drowsy, may develop seizures due to cerebral venous disease.

Hepatic venous thrombosis will present with abdominal distension(ascites), features of liver insufficiency like nausea, vomiting, loss of appetite, yellowish discoloration of eyes, generalized swelling and gastrointestinal bleeding( either as haematemesis/ malena).

Renal vein thrombosis will manifest as loin/ back pain, reduced urine out put and haematuria like symptoms.

Mesenteric vein thrombosis will present as abdominal pain and altered bowel habits. In severe ischemic condition bowel ischemia can progress in to bowel perforation causing an acute abdomen.

Retinal vein thrombosis leads to vision problems.
Symptoms suggestive of other venous thrombosis
Though these presentations are uncommon patients can develop thrombus in other venous systems.
eg;
Cerebral venous thrombosis patient will be confused, drowsy, may develop seizures due to cerebral venous disease.

Hepatic venous thrombosis will present with abdominal distension(ascites), features of liver insufficiency like nausea, vomiting, loss of appetite, yellowish discoloration of eyes, generalized swelling and gastrointestinal bleeding( either as haematemesis/ malena).

Renal vein thrombosis will manifest as loin/ back pain, reduced urine out put and haematuria like symptoms.

Mesenteric vein thrombosis will present as abdominal pain and altered bowel habits. In severe ischemic condition bowel ischemia can progress in to bowel perforation causing an acute abdomen.

Retinal vein thrombosis leads to vision problems.
Past gynacological & obstetric history related to complications of pregnancy Due to the hypercoagulability state these patient can present with/ may have past history of recurrent miscarriages, intra uterine deaths, still births, pre-eclamsia, placental abruption. Past gynacological & obstetric history related to complications of pregnancy
Due to the hypercoagulability state these patient can present with/ may have past history of recurrent miscarriages, intra uterine deaths, still births, pre-eclamsia, placental abruption.
History of sudden onset skin rash (red patches/ brising, skin discoloration) associated with severe ill health. Purpura fulminans can develop in these patients and it can finally lead to skin necrosis (due to thrombi formation in small vessels supplying to skin) and disseminated intravascular coagulation. History of sudden onset skin rash (red patches/ brising, skin discoloration) associated with severe ill health.
Purpura fulminans can develop in these patients and it can finally lead to skin necrosis (due to thrombi formation in small vessels supplying to skin) and disseminated intravascular coagulation.
History suggestive of arterial thrombosis There are not much strong evidence to say this condition is associated with arterial thrombosis. But due to the hypercoagulability state it can increased risk of thrombotic complications. Arterial thrombotic complications can damage various systems giving specific features of hypoperfusion.
Eg; In cardiac complications, patient will present with chest pain, difficulty in bresthing, dizziness, sweating and other features of myocardial infarction/ angina.

If thrombotic complications occur in central nervous system, patient will have seizures, paralysis and paresthesia like features.

If thrombosis occur in a artery supplying to limbs, patients will present with acute limb ischemia (sever pain at rest, coldness, limited movements, numbness) following features of occlusive arterial disease like pain starting few minutes after initiating walking, pain relief with resting and reproduce with walking in a same distance.

Thrombosis in pulmonary arteries will give features like chest pain, difficulty in breathing, cough and wheezing.

Retinal artery thrombosis can leads to sudden onset loss of vision while small thrombi may present with transient loss of vision (amaurosis fugax).
History suggestive of arterial thrombosis
There are not much strong evidence to say this condition is associated with arterial thrombosis. But due to the hypercoagulability state it can increased risk of thrombotic complications. Arterial thrombotic complications can damage various systems giving specific features of hypoperfusion.
Eg; In cardiac complications, patient will present with chest pain, difficulty in bresthing, dizziness, sweating and other features of myocardial infarction/ angina.

If thrombotic complications occur in central nervous system, patient will have seizures, paralysis and paresthesia like features.

If thrombosis occur in a artery supplying to limbs, patients will present with acute limb ischemia (sever pain at rest, coldness, limited movements, numbness) following features of occlusive arterial disease like pain starting few minutes after initiating walking, pain relief with resting and reproduce with walking in a same distance.

Thrombosis in pulmonary arteries will give features like chest pain, difficulty in breathing, cough and wheezing.

Retinal artery thrombosis can leads to sudden onset loss of vision while small thrombi may present with transient loss of vision (amaurosis fugax).
History of presence of risk factors for thrombosis There are some well known modifiable/ acquired risk factors for development of arterial and venous thrombosis. Presence of these conditions need to be identify as it is important in management.
Risk factors for the development of arterial thrombi are smoking, hypertension, hyperlipidaemia, diabetes mellitus, polycythemia and connective tissue disorders like SLE, APLS.

Risk factors for the development of venous thrombi are surgery, trauma, immobilization, pregnancy, use of oral contraceptive pills, hormone replacement therapy, obesity, varicose veins and presence of systemic conditions (heart failure, malignancy, nephrotic syndrome)..
History of presence of risk factors for thrombosis
There are some well known modifiable/ acquired risk factors for development of arterial and venous thrombosis. Presence of these conditions need to be identify as it is important in management.
Risk factors for the development of arterial thrombi are smoking, hypertension, hyperlipidaemia, diabetes mellitus, polycythemia and connective tissue disorders like SLE, APLS.

Risk factors for the development of venous thrombi are surgery, trauma, immobilization, pregnancy, use of oral contraceptive pills, hormone replacement therapy, obesity, varicose veins and presence of systemic conditions (heart failure, malignancy, nephrotic syndrome)..
Family history of similer symptoms primary thrombocytopenia is occur following inherited conditions. So there will be Family history of similer symptoms especially young relatives with recurrent spontaneous thrombosis. Family history of similer symptoms
primary thrombocytopenia is occur following inherited conditions. So there will be Family history of similer symptoms especially young relatives with recurrent spontaneous thrombosis.

Clinicals - Examination

Fact Explanation
General examination ill health (appearance of the illness will give an rough idea about the level of severity of the illness), pain (this will help in managing the patient),temperature ( this will be important in excluding the differentials like cellulitis and pyrexia will be a symtom in thrombosis like pulmonary embolism), icterus (icterus will be a symptom in associated hepatic vein thrombosis) and level of hydration of the patient.

There will be a skin rash (purpura fulminans) with petechiae and ecchimotic patches. In severe condition there will be skin necrosis causing skin discoloration. There will be features of disseminated intravascular coagulation, like extensive bruising and increased bleeding tendency (eg: spontaneous haematuria, gum bleeding, nasal bleeding, puncture site bleeding).
General examination
ill health (appearance of the illness will give an rough idea about the level of severity of the illness), pain (this will help in managing the patient),temperature ( this will be important in excluding the differentials like cellulitis and pyrexia will be a symtom in thrombosis like pulmonary embolism), icterus (icterus will be a symptom in associated hepatic vein thrombosis) and level of hydration of the patient.

There will be a skin rash (purpura fulminans) with petechiae and ecchimotic patches. In severe condition there will be skin necrosis causing skin discoloration. There will be features of disseminated intravascular coagulation, like extensive bruising and increased bleeding tendency (eg: spontaneous haematuria, gum bleeding, nasal bleeding, puncture site bleeding).
Limb examination for deep vein thrombosis If the patient present with limb pain limb examination need to be done. In DVT limb will be swollen, red and very tender. patient will have limited movements due to the pain. Limb examination for deep vein thrombosis
If the patient present with limb pain limb examination need to be done. In DVT limb will be swollen, red and very tender. patient will have limited movements due to the pain.
Respiratory system examination for pulmonary embolism patient will be febrile, cyanosed, dyspnoic, coughing, wheezing, sputum will be blood staining. Jvp can be elevated. There will pleural rub and pleural effusion on lung examination. Respiratory system examination for pulmonary embolism
patient will be febrile, cyanosed, dyspnoic, coughing, wheezing, sputum will be blood staining. Jvp can be elevated. There will pleural rub and pleural effusion on lung examination.
Central nervous system examination Either with cerebral venous thrombosis or arterial thrombi formation, patients can develop neurological symptoms. On examination patient will be confused, drowsy, may develop seizures and there will be motor/ sensory involvement or signs of imbalance with cerebellar involvement. Central nervous system examination
Either with cerebral venous thrombosis or arterial thrombi formation, patients can develop neurological symptoms. On examination patient will be confused, drowsy, may develop seizures and there will be motor/ sensory involvement or signs of imbalance with cerebellar involvement.
Abdominal examination There will be icterus, generalized oedema, ascites with hepatic vein thrombosis.

In mesenteric ischemia there will be tender abdomen and with perforation there will be garding and rigidity.

In renal vein thrombosis there will be haematuria on urine examination and patients will have generalized oedema.
Abdominal examination
There will be icterus, generalized oedema, ascites with hepatic vein thrombosis.

In mesenteric ischemia there will be tender abdomen and with perforation there will be garding and rigidity.

In renal vein thrombosis there will be haematuria on urine examination and patients will have generalized oedema.
Fundoscopic examination Stormy sunset can be seen in central retinal vein occlusion. wedge changes ( tortuous veins, oedema) are occur in branched retinal vein occlusion.
Retinal haemorrhages, disk pallor and oedema can be seen in retinal artery occlusion..
Fundoscopic examination
Stormy sunset can be seen in central retinal vein occlusion. wedge changes ( tortuous veins, oedema) are occur in branched retinal vein occlusion.
Retinal haemorrhages, disk pallor and oedema can be seen in retinal artery occlusion..
Gynaecological and obstetric examination In miscarriages/ there will be per vaginal bleeding, pains and OS can be opened/ closed.
In a placental abruption patient may be haemodynamically unstable (shock), PV bleeding will present. Uterus will be tender.
In an intra uterine deaths foetal movements and foetal heart sound will be absent.
Pre-eclamsia, Patient will have hypertension, generalized body swelling and urine examination will reveal proteinuria.
Gynaecological and obstetric examination
In miscarriages/ there will be per vaginal bleeding, pains and OS can be opened/ closed.
In a placental abruption patient may be haemodynamically unstable (shock), PV bleeding will present. Uterus will be tender.
In an intra uterine deaths foetal movements and foetal heart sound will be absent.
Pre-eclamsia, Patient will have hypertension, generalized body swelling and urine examination will reveal proteinuria.

Investigations - Diagnosis

Fact Explanation
Full Blood count To detect any polycythemia/ anaemia assocciated with, WBC counts and Platelet counts will also helpful in deciding the diagnosis. Full Blood count
To detect any polycythemia/ anaemia assocciated with, WBC counts and Platelet counts will also helpful in deciding the diagnosis.
ESR/ CRP These inflammatory markers will also useful in identifying any ongoing inflammmatory condition. ESR/ CRP
These inflammatory markers will also useful in identifying any ongoing inflammmatory condition.
Blood film This will be useful in excluding malignancies like myeloproliferative disorder and other differential diagnosis like sickle cell disease. Blood film
This will be useful in excluding malignancies like myeloproliferative disorder and other differential diagnosis like sickle cell disease.
Thrombin time and reptilase test This will assess the fibrinogen activity and these tests will be prolonged in the abnormal fibrinogen activity. Thrombin time and reptilase test
This will assess the fibrinogen activity and these tests will be prolonged in the abnormal fibrinogen activity.
Prothrombin time and APTT tests will assess the clotting status/ clotting factor activity of the patient. these will be shorten in Thrombophilia. Prothrombin time and APTT
tests will assess the clotting status/ clotting factor activity of the patient. these will be shorten in Thrombophilia.
Activated protein C resistance test and DNA analysis (PCR) These tests will assess the factor V Leiden as factor V Leiden gene mutation (activated protein C resistance) is the most common inherited cause of venous thrombosis. Activated protein C resistance test and DNA analysis (PCR)
These tests will assess the factor V Leiden as factor V Leiden gene mutation (activated protein C resistance) is the most common inherited cause of venous thrombosis.
Protein C and protein S immunological assay These are to assess any protein C and/ or protein S deficiency. Protein C and protein S immunological assay
These are to assess any protein C and/ or protein S deficiency.
Prothrombin gene analysis Prothrombin allele G20210A is a condition with increased levels of prothrombin. Prothrombin gene analysis will useful in assessing the presence of this condition. This condition will also have high levels of factor VIII, IX and XI . Prothrombin gene analysis
Prothrombin allele G20210A is a condition with increased levels of prothrombin. Prothrombin gene analysis will useful in assessing the presence of this condition. This condition will also have high levels of factor VIII, IX and XI .
Plasma homocysteine estimation In hyperhomocycteinaemia, there will be higher levels of plasma homocycteinse. Plasma homocysteine estimation
In hyperhomocycteinaemia, there will be higher levels of plasma homocycteinse.
Test for CD59 and CD55 expression This tests will be useful in excluding the differencial diagnosis, paroxysmal nocturnal haemoglobinuria. Test for CD59 and CD55 expression
This tests will be useful in excluding the differencial diagnosis, paroxysmal nocturnal haemoglobinuria.
Lupus anticoagulant assay and anticardiolipin antibody and anti-β2 glycoprotein 1 antibody This will assess the prothrombotic status of the patient. Lupus anticoagulant assay and anticardiolipin antibody and anti-β2 glycoprotein 1 antibody
This will assess the prothrombotic status of the patient.
fibrinogen tests, factor VIII, plasminogen and factor XII levels High levels of fibrinogen, and other clotting factors can associated with arterial thrombosis. fibrinogen tests, factor VIII, plasminogen and factor XII levels
High levels of fibrinogen, and other clotting factors can associated with arterial thrombosis.
Antithrombin immunological and functional assay (cromogenic heparin cofactor assay) This is helpful in assessing antithrombin III deficiency. Antithrombin immunological and functional assay (cromogenic heparin cofactor assay)
This is helpful in assessing antithrombin III deficiency.

Investigations - Management

Fact Explanation
Plasma D dimer concentration This is useful in diagnosis of the Deep vein thrombosis and assess the risk of developing pulmonary embolism. Plasma D dimer concentration
This is useful in diagnosis of the Deep vein thrombosis and assess the risk of developing pulmonary embolism.
PT/ INR This is useful in patients on anticoagulants.
According to target levels recommended by the British Society for Haematology (2000),
Target INR is 2.0-3.0 : treatment of DVT, Pulmonary embolism, atrial fibrilation, recurrent DVT off warfarin; symptomatic inherited thrombophilia, cardiomyopathy, mural thrombus, cardioversion

Target INR is 3.0-4.0 : recurrent DVT while on warfarin, mechanical prosthetic heart valve, APLs.
PT/ INR
This is useful in patients on anticoagulants.
According to target levels recommended by the British Society for Haematology (2000),
Target INR is 2.0-3.0 : treatment of DVT, Pulmonary embolism, atrial fibrilation, recurrent DVT off warfarin; symptomatic inherited thrombophilia, cardiomyopathy, mural thrombus, cardioversion

Target INR is 3.0-4.0 : recurrent DVT while on warfarin, mechanical prosthetic heart valve, APLs.
Serial compression ultrasound combine with colour doppler/ duplex scan This is useful in investigating a patient with DVT. This will assess the exact site and size of the thrombus. Serial compression ultrasound combine with colour doppler/ duplex scan
This is useful in investigating a patient with DVT. This will assess the exact site and size of the thrombus.
Contrast venography This is useful in patients who are clinically suspicious as having DVT but ultrasound examination is normal. This is the most sensitive investigation in diagnosis of DVT. In here X ray views are taken after injecting a contrast medum. Contrast venography
This is useful in patients who are clinically suspicious as having DVT but ultrasound examination is normal. This is the most sensitive investigation in diagnosis of DVT. In here X ray views are taken after injecting a contrast medum.
Chest X ray In a suspecting case of pulmonary embolism chest X ray will be useful. There may be evidence of pulmonary infarctions. Chest X ray
In a suspecting case of pulmonary embolism chest X ray will be useful. There may be evidence of pulmonary infarctions.
MRI This is useful in assessing both venous and arterial thrombosis ( eg; cerebral venous thrombosis/ strokes, renal vein occlusion, hepatic vein occlusion). MRI
This is useful in assessing both venous and arterial thrombosis ( eg; cerebral venous thrombosis/ strokes, renal vein occlusion, hepatic vein occlusion).
Ventilation perfusion (VQ) scintigraphy Useful in pulmonary embolism and with this look for the perfusion defects with no corresponding ventilation defects. Ventilation perfusion (VQ) scintigraphy
Useful in pulmonary embolism and with this look for the perfusion defects with no corresponding ventilation defects.
Computer tomography pulmonary angiography This is the 1st line investigation in diagnosing pulmonary embolism. It shows the anatomy of pulmonary arteries. Computer tomography pulmonary angiography
This is the 1st line investigation in diagnosing pulmonary embolism. It shows the anatomy of pulmonary arteries.
pulmonary angiography/ MRI pulmonary angiography These tests also use in diagnosing pulmonary embolism. pulmonary angiography/ MRI pulmonary angiography
These tests also use in diagnosing pulmonary embolism.
ECG/ Echocardiogram In severe cases of pulmonary embolism, there will be right heart strain. This can be diagnose with Echocardiogram. Also useful in assessing the thrombotic complications affecting the cardiac vessels (eg; myocardial innfarction). ECG/ Echocardiogram
In severe cases of pulmonary embolism, there will be right heart strain. This can be diagnose with Echocardiogram. Also useful in assessing the thrombotic complications affecting the cardiac vessels (eg; myocardial innfarction).
Ultrasound scan This will be useful in assessing thrombotic complications like in gynaecological and obstetric complications (recurrent miscarriages, placenta previa, intra uterine death, pre eclampsis) to assess the foetal weii being and in hepatic vein thrombosis, to assess ascites. Ultrasound scan
This will be useful in assessing thrombotic complications like in gynaecological and obstetric complications (recurrent miscarriages, placenta previa, intra uterine death, pre eclampsis) to assess the foetal weii being and in hepatic vein thrombosis, to assess ascites.
Fasting blood sugar level This is to assess the blood sugar levels of the patient as it can further progress the thrombotic complications Fasting blood sugar level
This is to assess the blood sugar levels of the patient as it can further progress the thrombotic complications
Lipid profile test As hperlipidaemia can cause secondary thrombophilia, this test alsom useful in assessing the fitness of the patient. Lipid profile test
As hperlipidaemia can cause secondary thrombophilia, this test alsom useful in assessing the fitness of the patient.
Renal function tests including UFR, serum creatinine, blood urea and serum elcetrolytes Nephrotic syndrome can predispose to hypercoagulability these tests are useful. Aslo important in assessing the thrombotic complications causing renal vein thrombosis. These are useful in assessing the renal function prior to contrast medicated investigations as well. Renal function tests including UFR, serum creatinine, blood urea and serum elcetrolytes
Nephrotic syndrome can predispose to hypercoagulability these tests are useful. Aslo important in assessing the thrombotic complications causing renal vein thrombosis. These are useful in assessing the renal function prior to contrast medicated investigations as well.
ECG/ echocardiogram Heart failure is another secondary cause for thrombophilia. So these tests will assess the cardiac function of the patients. ECG/ echocardiogram
Heart failure is another secondary cause for thrombophilia. So these tests will assess the cardiac function of the patients.
Indications for screening a patient for thrombophilia Screening for thromboplilia with special tests is indicated in patients with,
1) Arterial thrombosis in patients less than 50 years of age (screen for APLS)
2) Venous thrombosis in patients less than 40 years of age with no risk factors
3) Unexplained recurrent venous thrombo embolism
4) Thrombi formation in unusual sites like mesenteric vein thrombosis, portal vein thrombosis
5) Familial venous thrombo embolism
6) Venous thrombo embolism with oral contraceptives/ pregnancy
7) Recurrent miscarriages (3 or more)
8) Neonatal thrombosis
Indications for screening a patient for thrombophilia
Screening for thromboplilia with special tests is indicated in patients with,
1) Arterial thrombosis in patients less than 50 years of age (screen for APLS)
2) Venous thrombosis in patients less than 40 years of age with no risk factors
3) Unexplained recurrent venous thrombo embolism
4) Thrombi formation in unusual sites like mesenteric vein thrombosis, portal vein thrombosis
5) Familial venous thrombo embolism
6) Venous thrombo embolism with oral contraceptives/ pregnancy
7) Recurrent miscarriages (3 or more)
8) Neonatal thrombosis
Staging the various hereditary (familial or primary) thrombophilia types according to the supportive data available. Conditions with strongly supportive data:
-Antithrombin, Protein C, Protein S deficiency
-Activated protein C resistance
-Factor V Leiden
-Prothrombin G20210A
-Homocystinuria

Conditions with supportive Data:
-Increased plasma factors I (fibrinogen), II (prothrombin), VIII, IX, XI
-Factor XIII polymorphisms
-Hyperhomocysteinemia
-Dysfibrinogenemia
-Reduced tissue factor pathway inhibitor

Conditions with weakly supportive Data:
-Reduced protein Z and Z-dependent protease inhibitor
-Tissue plasminogen activator deficiency
-Increased plasminogen activator inhibitor (PAI)-1
-Increased thrombin-activatable fibrinolysis inhibitor
-Hypoplasminogenemia and dysplasminogenemia
-Hypofibrinolysis
Staging the various hereditary (familial or primary) thrombophilia types according to the supportive data available.
Conditions with strongly supportive data:
-Antithrombin, Protein C, Protein S deficiency
-Activated protein C resistance
-Factor V Leiden
-Prothrombin G20210A
-Homocystinuria

Conditions with supportive Data:
-Increased plasma factors I (fibrinogen), II (prothrombin), VIII, IX, XI
-Factor XIII polymorphisms
-Hyperhomocysteinemia
-Dysfibrinogenemia
-Reduced tissue factor pathway inhibitor

Conditions with weakly supportive Data:
-Reduced protein Z and Z-dependent protease inhibitor
-Tissue plasminogen activator deficiency
-Increased plasminogen activator inhibitor (PAI)-1
-Increased thrombin-activatable fibrinolysis inhibitor
-Hypoplasminogenemia and dysplasminogenemia
-Hypofibrinolysis
Genetic screening Patients and family members of the patients who are having recurrent spontaneous thrombotic complications can under go genetic screening for various causes of primary thrombophilia. The way of inheritence and the risk of genetic transmission should be discussed with patients. Genetic screening
Patients and family members of the patients who are having recurrent spontaneous thrombotic complications can under go genetic screening for various causes of primary thrombophilia. The way of inheritence and the risk of genetic transmission should be discussed with patients.

Management - Supportive

Fact Explanation
Health education The patient should be thoroughly educated regarding the disease, aetiology, complications associated with, early identification of complications, investigation and treatment options available. Health education
The patient should be thoroughly educated regarding the disease, aetiology, complications associated with, early identification of complications, investigation and treatment options available.
Prevention/ minimize of thrombi formation Patient education and close monitoring of the thrombotic complications is very important. Prophylactic measures are very important here.

eg: Prevent DVT: DVT prophylaxis can be non pharmacological and pharmacology modalities. Non pharmacological moralities are good hydration, adequate mobilization of the patient, limb physiotherapy and thrombo embolic detergenic stocking. The main pharmacological propylaxis is low molecular weight heparin in high risk patients if no contraindication (eg: Sub cutaneous enoxaparin 0.5mg/kg/day).
Prevention/ minimize of thrombi formation
Patient education and close monitoring of the thrombotic complications is very important. Prophylactic measures are very important here.

eg: Prevent DVT: DVT prophylaxis can be non pharmacological and pharmacology modalities. Non pharmacological moralities are good hydration, adequate mobilization of the patient, limb physiotherapy and thrombo embolic detergenic stocking. The main pharmacological propylaxis is low molecular weight heparin in high risk patients if no contraindication (eg: Sub cutaneous enoxaparin 0.5mg/kg/day).
Modification of co-existing acquired risk factors Patient should be advised regarding the secondary causes of thrombipilia as there are some well known modifiable/ acquired risk factors for development of arterial and venous thrombosis.
Risk factors for the development of arterial thrombi are smoking, hypertension, hyperlipidaemia, diabetes mellitus, polycythemia and connective tissue disorders like SLE, APLS.Risk factors for the development of venous thrombi are surgery, trauma, immobilization, pregnancy, use of oral contraceptive pills, hormone replacement therapy, obesity, varicose veins and presence of systemic conditions (heart failure, malignancy, nephrotic syndrome). these risk factors nees to be identify and removal/ control need to be done .
Eg: Changing to an other contraceptive method from oral contraceptive pills.
Control hypertension, hyperlipidaemia and diabetes
Early mobilization after syrgery, prophylaxia LMW heparin, compression stockings to prevent DVT.
Maintain average body weight.
Modification of co-existing acquired risk factors
Patient should be advised regarding the secondary causes of thrombipilia as there are some well known modifiable/ acquired risk factors for development of arterial and venous thrombosis.
Risk factors for the development of arterial thrombi are smoking, hypertension, hyperlipidaemia, diabetes mellitus, polycythemia and connective tissue disorders like SLE, APLS.Risk factors for the development of venous thrombi are surgery, trauma, immobilization, pregnancy, use of oral contraceptive pills, hormone replacement therapy, obesity, varicose veins and presence of systemic conditions (heart failure, malignancy, nephrotic syndrome). these risk factors nees to be identify and removal/ control need to be done .
Eg: Changing to an other contraceptive method from oral contraceptive pills.
Control hypertension, hyperlipidaemia and diabetes
Early mobilization after syrgery, prophylaxia LMW heparin, compression stockings to prevent DVT.
Maintain average body weight.
Management in an emergency situation The possible emergencies in patients with thrombophilia are pulmonary embolism, stoke, myocardial infarction, cerebral venous thrombosis, mesenteric infarction. In these circumstances ABC management is essentially life saving. Airway has to be secured, breathing has to be assessed and respiratory support should be given. Circulation has to be assessed and fluid resuscitation with inotrope support has to started as indicated. Management in an emergency situation
The possible emergencies in patients with thrombophilia are pulmonary embolism, stoke, myocardial infarction, cerebral venous thrombosis, mesenteric infarction. In these circumstances ABC management is essentially life saving. Airway has to be secured, breathing has to be assessed and respiratory support should be given. Circulation has to be assessed and fluid resuscitation with inotrope support has to started as indicated.

Management - Specific

Fact Explanation
Deep vein thrombosis management LMWH (eg; enoxaparin 20mg/24 hours, sub cutaneously) can be given but in severe ileofemoral thrombi will need unfrationated heparin. Stary warfarin with the heparin and continue while heparin can be stopped with INR 2-3. Warfarin need to continue for 6 months as in Primary Thrombophilia no cause can be found. Deep vein thrombosis management
LMWH (eg; enoxaparin 20mg/24 hours, sub cutaneously) can be given but in severe ileofemoral thrombi will need unfrationated heparin. Stary warfarin with the heparin and continue while heparin can be stopped with INR 2-3. Warfarin need to continue for 6 months as in Primary Thrombophilia no cause can be found.
Pulmonary embolism management In an massive pulmonary embolism,
1) 100% oxygen need to be given after ensuring the patent air way
2) For pain management IV morphine 10 mg can be given with antiemetics
3) Cannulate with a wide bore needle and send blood for investigations (eg; PT/INR) and give IV heparin bolus followed by 18u/kg/hour with the guidence of APTT.
4) If the systolic blood pressure more than 90mmHg, start warfarin 10mh/24 hours orally.
5) if the systolic blood pressure less than 90mmHg, give colloid infusion, then dobutamine (after 500 ml of colloid) and finally noradrenaline to pick up the blood pressure and continue warfarin as above.
6) Finally confirm the diagnosis with investigations.

Placement of vana caval filtration will be useful in patients with emboli development despit of anticoagulation
Pulmonary embolism management
In an massive pulmonary embolism,
1) 100% oxygen need to be given after ensuring the patent air way
2) For pain management IV morphine 10 mg can be given with antiemetics
3) Cannulate with a wide bore needle and send blood for investigations (eg; PT/INR) and give IV heparin bolus followed by 18u/kg/hour with the guidence of APTT.
4) If the systolic blood pressure more than 90mmHg, start warfarin 10mh/24 hours orally.
5) if the systolic blood pressure less than 90mmHg, give colloid infusion, then dobutamine (after 500 ml of colloid) and finally noradrenaline to pick up the blood pressure and continue warfarin as above.
6) Finally confirm the diagnosis with investigations.

Placement of vana caval filtration will be useful in patients with emboli development despit of anticoagulation
Management of complications of the treatment Eg: warfarin over dose
According to British Commitee for standards Haematology,

INR 3.0-6.0 ; warfarin dose need to be reduce/ stopped (target INR 2.5)

INR 4.0-6.0 ; warfarin can re start with INR less than 5.0 ( target INR 3.5)

INR 6.0-8.0 with no/ minor bleeding; stop warfarin and re start with INR less than 5.0

INR more than 8.0 with no/ minor bleeding; stop warfarin and re start with INR less than 5.0. If other risk factors for bleeding is present give 0.5-2.5 Vitamin K orally

Major bleeding; stop warfarin, give prothrombin complex concentrates 50U/Kg in preference, Give FFP 15ml/Kg when available and give IV/ oral Vitamin K 5mg.
Management of complications of the treatment
Eg: warfarin over dose
According to British Commitee for standards Haematology,

INR 3.0-6.0 ; warfarin dose need to be reduce/ stopped (target INR 2.5)

INR 4.0-6.0 ; warfarin can re start with INR less than 5.0 ( target INR 3.5)

INR 6.0-8.0 with no/ minor bleeding; stop warfarin and re start with INR less than 5.0

INR more than 8.0 with no/ minor bleeding; stop warfarin and re start with INR less than 5.0. If other risk factors for bleeding is present give 0.5-2.5 Vitamin K orally

Major bleeding; stop warfarin, give prothrombin complex concentrates 50U/Kg in preference, Give FFP 15ml/Kg when available and give IV/ oral Vitamin K 5mg.
Fibrinolytic agents Fibrinolytic agents like Streptokinase, tissue plasminogen activator, single chain urokinase type plasminogen activator and acylated plasminogen streptokinase activator complex can be given in acute myocardial infarction, major pulmonary embolism and acute peripheral arterial occlusion. Fibrinolytic agents
Fibrinolytic agents like Streptokinase, tissue plasminogen activator, single chain urokinase type plasminogen activator and acylated plasminogen streptokinase activator complex can be given in acute myocardial infarction, major pulmonary embolism and acute peripheral arterial occlusion.
Antiplatelet drugs These drugs ( aspirin, clopodogrel, abcximab) are proven to be useful in secondary prevention of vascular thrombotic events. Antiplatelet drugs
These drugs ( aspirin, clopodogrel, abcximab) are proven to be useful in secondary prevention of vascular thrombotic events.

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