Anticardiolipin syndrome

Hematology

Clinicals - History

Fact Explanation
Swollen, reddened limb (unilateral or bilateral) Antiphospholipid syndrome is a disease with following features: arterial or venous thrombosis, recurrent miscarriages occur in a person, laboratory tests positive for antiphospholipid antibodies. The most frequent manifestation in this syndrome is deep vein thrombosis.This is part of diagnosing criteria. This occurs due to transudation of fluid following the venous obstruction and congestion of blood in the affected region. Swollen, reddened limb (unilateral or bilateral)
Antiphospholipid syndrome is a disease with following features: arterial or venous thrombosis, recurrent miscarriages occur in a person, laboratory tests positive for antiphospholipid antibodies. The most frequent manifestation in this syndrome is deep vein thrombosis.This is part of diagnosing criteria. This occurs due to transudation of fluid following the venous obstruction and congestion of blood in the affected region.
Pain and tenderness in the calf of the swollen limbs The most frequent manifestation in this syndrome is deep vein thrombosis. This occurs due to transudation of fluid following the venous obstruction and congestion of blood in the affected region. Pain and tenderness in the calf of the swollen limbs
The most frequent manifestation in this syndrome is deep vein thrombosis. This occurs due to transudation of fluid following the venous obstruction and congestion of blood in the affected region.
Acutely developing varicose veins This can be a presentation of DVT. This is due to the opening of collateral veins. Acutely developing varicose veins
This can be a presentation of DVT. This is due to the opening of collateral veins.
Severe pain and the onset numbness of the affected limb This is due to compartment syndrome created by the increasing pressure resulting in reduced arterial flow causing limb threatening ischemia. Severe pain and the onset numbness of the affected limb
This is due to compartment syndrome created by the increasing pressure resulting in reduced arterial flow causing limb threatening ischemia.
Sudden onset dyspnoea This is due to pulmonary embolism. The thrombi in the limbs and distal veins get dislodged and obstructs the pulmonary arteries.
This can be due to a rare complication of respiratory distress syndrome following Pulmonary capillaritis.
Sudden onset dyspnoea
This is due to pulmonary embolism. The thrombi in the limbs and distal veins get dislodged and obstructs the pulmonary arteries.
This can be due to a rare complication of respiratory distress syndrome following Pulmonary capillaritis.
Haemoptisis. This is a feature of a larger PE .This occurs due to ruptured pulmonary vessels due to increased pressure. Haemoptisis.
This is a feature of a larger PE .This occurs due to ruptured pulmonary vessels due to increased pressure.
Sudden onset chest pain. This is due to pulmonary embolism .The thrombi in the limbs and distal veins get dislodged and obstructs the pulmonary arteries. Sudden onset chest pain.
This is due to pulmonary embolism .The thrombi in the limbs and distal veins get dislodged and obstructs the pulmonary arteries.
Sudden onset Syncope This is a feature of PE .This occurs due to reduced cardiac output and diminished cerebral flow. Sudden onset Syncope
This is a feature of PE .This occurs due to reduced cardiac output and diminished cerebral flow.
Sudden onset limb weakness, Difficulty in speech, difficulty in swallowing This due to a cerebrovascular accident (ischemic stroke). Arterial thrombosis is presented in this manner. Valvular damage, vegetation like growth and embolisation can cause strokes. Limb weakness and paresthesia and sphincter dysfunction can be the result of transverse myelopathy (an interaction between aPL and cellular components). Arterial thrombi is part of diagnosing criteria. Sudden onset limb weakness, Difficulty in speech, difficulty in swallowing
This due to a cerebrovascular accident (ischemic stroke). Arterial thrombosis is presented in this manner. Valvular damage, vegetation like growth and embolisation can cause strokes. Limb weakness and paresthesia and sphincter dysfunction can be the result of transverse myelopathy (an interaction between aPL and cellular components). Arterial thrombi is part of diagnosing criteria.
Visual disturbance Visual disturbance is due to obstruction of retinal arteries due to thrombosis. Visual disturbance
Visual disturbance is due to obstruction of retinal arteries due to thrombosis.
Headache Headache can be a feature due to ischemia following thrombosis. Headache
Headache can be a feature due to ischemia following thrombosis.
Obstetric complications: Early and late fetal losses, premature births Early and late fetal losses, premature births frequent fetal and obstetric manifestations. There are few mechanisms in the pathophysiology. Thrombosis, complement activation and imbalanced angiogenesis Following 3 facts are in the diagnosing criteria: one or more unexplained events of following 2; loss of morphologically normal fetus( more than 10th week of gestation), premature births of a normal neonate before the 34th week of gestation( due to eclampsia, pre-eclampsia), three or more and unexplained event of following and consecutive spontaneous abortions before the 10th week of gestation Obstetric complications: Early and late fetal losses, premature births
Early and late fetal losses, premature births frequent fetal and obstetric manifestations. There are few mechanisms in the pathophysiology. Thrombosis, complement activation and imbalanced angiogenesis Following 3 facts are in the diagnosing criteria: one or more unexplained events of following 2; loss of morphologically normal fetus( more than 10th week of gestation), premature births of a normal neonate before the 34th week of gestation( due to eclampsia, pre-eclampsia), three or more and unexplained event of following and consecutive spontaneous abortions before the 10th week of gestation
Obstetric complications: Pre-eclampsia Pre-eclampsia is a frequent obstetric complication. , There are few mechanisms in the pathophysiology. Thrombosis, complement activation and imbalanced angiogenesis. Obstetric complications: Pre-eclampsia
Pre-eclampsia is a frequent obstetric complication. , There are few mechanisms in the pathophysiology. Thrombosis, complement activation and imbalanced angiogenesis.
Dyspnoea, Orthopnoea, and paroxysmal nocturnal dyspnoea This can be the result of myocardial infarction following thrombosis, valvular incompetence( ex-mitral, ) Dyspnoea, Orthopnoea, and paroxysmal nocturnal dyspnoea
This can be the result of myocardial infarction following thrombosis, valvular incompetence( ex-mitral, )
Cutaneous manifestations: Livedo reticularis This occurs due to immune complex deposition inside dermal vessels. Cutaneous manifestations: Livedo reticularis
This occurs due to immune complex deposition inside dermal vessels.
Anuria or oliguria This is due to renal failure following thrombosis of renal vessels. Anuria or oliguria
This is due to renal failure following thrombosis of renal vessels.
Severe sepsis like symptoms ( i.e. altered consciousness, collapse) This is due to catastrophic Antiphospholipid Syndrome (systemic inflammatory response syndrome, due to excessive cytokine release from necrotic tissues). This is characterized by multiple microvascular thrombosis and multiorgan failure. Severe sepsis like symptoms ( i.e. altered consciousness, collapse)
This is due to catastrophic Antiphospholipid Syndrome (systemic inflammatory response syndrome, due to excessive cytokine release from necrotic tissues). This is characterized by multiple microvascular thrombosis and multiorgan failure.
Risk factors associated in developing aPLS Autoimmune conditions (SLE ,Sjogren's syndrome), past history of syphilis, HIV/AIDS, Lyme disease or Hepatitis C, history of using drugs such as hydralazine, quinidine, phenytoin ,amoxicillin or a positive family history. Risk factors associated in developing aPLS
Autoimmune conditions (SLE ,Sjogren's syndrome), past history of syphilis, HIV/AIDS, Lyme disease or Hepatitis C, history of using drugs such as hydralazine, quinidine, phenytoin ,amoxicillin or a positive family history.
Risk factors associated in developing thrombosis. Factors such as pregnancy, immobility
smoking , hyperlipidemia, high BMIand oral contraceptive use can increase the risk of thrombus formation.
Risk factors associated in developing thrombosis.
Factors such as pregnancy, immobility
smoking , hyperlipidemia, high BMIand oral contraceptive use can increase the risk of thrombus formation.

Clinicals - Examination

Fact Explanation
Swollen erythematous limb This is present in specially lower limb thrombi. The most frequent manifestation in this syndrome is deep vein thrombosis. This occurs due to transudation of fluid following the venous obstruction and congestion of blood in the affected region. Swollen erythematous limb
This is present in specially lower limb thrombi. The most frequent manifestation in this syndrome is deep vein thrombosis. This occurs due to transudation of fluid following the venous obstruction and congestion of blood in the affected region.
Severe pain in the calf with passive dorsiflexion of the foot. This is positive Homan's sign.It is positive in deep vein thrombosis. The most frequent manifestation in this syndrome is deep vein thrombosis. Severe pain in the calf with passive dorsiflexion of the foot.
This is positive Homan's sign.It is positive in deep vein thrombosis. The most frequent manifestation in this syndrome is deep vein thrombosis.
Varicose veins This can be a presentation of DVT.this is due to the opening of collateral veins. Varicose veins
This can be a presentation of DVT.this is due to the opening of collateral veins.
Tachypnea This is a common sign in PE. This can be due to poor pulmonary circulation causing cerebral hypoxia and a reflex increase in the respiratory rate. Tachypnea
This is a common sign in PE. This can be due to poor pulmonary circulation causing cerebral hypoxia and a reflex increase in the respiratory rate.
Tachycardia This is a common sign in PE.Low cardiac output, pain and sympathetic activation can increase the heart rate. Tachycardia
This is a common sign in PE.Low cardiac output, pain and sympathetic activation can increase the heart rate.
Neck vein dilation This occurs in obstruction of the pulmonary arteries by the thrombus. Neck vein dilation
This occurs in obstruction of the pulmonary arteries by the thrombus.
Hypotension This is present in massive PE.This occurs due to reduced cardiac output following obstruction of the pulmonary arteries. Hypotension
This is present in massive PE.This occurs due to reduced cardiac output following obstruction of the pulmonary arteries.
Cyanosis This is present in massive PE.This occurs due to reduced pulmonary circulation and reduces oxygenation of blood. Cyanosis
This is present in massive PE.This occurs due to reduced pulmonary circulation and reduces oxygenation of blood.
Loud P2 on auscultation This is also a feature found in Pulmonary Embolism. Loud P2 on auscultation
This is also a feature found in Pulmonary Embolism.
Pansystolic murmur at the apex radiating to the axilla This is due to the regurgitant murmur of Mitral regurgitation. Pansystolic murmur at the apex radiating to the axilla
This is due to the regurgitant murmur of Mitral regurgitation.
In a pregnant female: Hypertension This can be due to Pregnancy induced hypertension caused by Antiphospholipid Syndrome. In a pregnant female: Hypertension
This can be due to Pregnancy induced hypertension caused by Antiphospholipid Syndrome.
In a pregnant female: Fundus less than dates This can be caused by placental thrombi resulting in placental insufficiency. In a pregnant female: Fundus less than dates
This can be caused by placental thrombi resulting in placental insufficiency.
Hemiplegia with increased tone and exaggerated reflexes. This due to a cerebrovascular accident. . Arterial thrombosis is presented in this manner. Valvular damage, vegetation like growth and embolisation can cause strokes. Hemiplegia with increased tone and exaggerated reflexes.
This due to a cerebrovascular accident. . Arterial thrombosis is presented in this manner. Valvular damage, vegetation like growth and embolisation can cause strokes.
Livedo reticularis This is a net-like, hyperpigmented and violaceous, appearance on the skin that occur due to changes in cutaneous circulation. Livedo reticularis
This is a net-like, hyperpigmented and violaceous, appearance on the skin that occur due to changes in cutaneous circulation.

Investigations - Diagnosis

Fact Explanation
Lupus Anticoagulant If Lupus Anticoagulant is present (detected according to the guidelines of International Society on Thrombosis and Haemostasis) on 2 occasions (12 weeks apart) the diagnosis of Antiphospholipid syndrome can be made. Lupus Anticoagulant
If Lupus Anticoagulant is present (detected according to the guidelines of International Society on Thrombosis and Haemostasis) on 2 occasions (12 weeks apart) the diagnosis of Antiphospholipid syndrome can be made.
Anticardiolipin antibody If Anticardiolipin antibody (IgG and/or IgM isotype) is present with titer greater than 40 GPL or MPL, or greater than the 99th percentile (measured by a standardized ELISA) in 2 occasions( 12 weeks apart) , then diagnosis of aPLS can be made. Anticardiolipin antibody
If Anticardiolipin antibody (IgG and/or IgM isotype) is present with titer greater than 40 GPL or MPL, or greater than the 99th percentile (measured by a standardized ELISA) in 2 occasions( 12 weeks apart) , then diagnosis of aPLS can be made.
Anti-beta2-glycoprotein-1 antibody If Anti-beta 2-glycoprotein-1 antibody ( IgG and/or IgM isotype)-is present in titer greater than the 99th percentile, (measured by a standardized ELISA test) in 2 occasions( 12 weeks apart) then diagnosis of aPLS can be made. Anti-beta2-glycoprotein-1 antibody
If Anti-beta 2-glycoprotein-1 antibody ( IgG and/or IgM isotype)-is present in titer greater than the 99th percentile, (measured by a standardized ELISA test) in 2 occasions( 12 weeks apart) then diagnosis of aPLS can be made.
Duplex scan of the legs This scan is commonly used to detect deep vein thrombosis, because in aPLS, the commonest presentation is Deep Vein Thrombosis. Duplex scan of the legs
This scan is commonly used to detect deep vein thrombosis, because in aPLS, the commonest presentation is Deep Vein Thrombosis.
Venography This scan is commonly used to detect deep vein thrombosis , because in aPLS, the commonest presentation is DVT. Venography
This scan is commonly used to detect deep vein thrombosis , because in aPLS, the commonest presentation is DVT.
Arterial angiograms Arterial thrombi can be presented with CNS symptoms or rarely with peripheral symptoms).This method is used in diagnosing arterial thrombi in both situations. Arterial angiograms
Arterial thrombi can be presented with CNS symptoms or rarely with peripheral symptoms).This method is used in diagnosing arterial thrombi in both situations.
Full blood count In some patients there can be a co-existent thrombocytopenia. Full blood count
In some patients there can be a co-existent thrombocytopenia.

Investigations - Management

Fact Explanation
PT-INR Long-term warfarin treatment needs monitoring of the PT- INR, the target range PT- INR is 2.0 to 3.0. PT-INR
Long-term warfarin treatment needs monitoring of the PT- INR, the target range PT- INR is 2.0 to 3.0.
Haemoglobin long-term warfarin treatment needs monitoring of hemoglobin levels to detect any asymptomatic decrease in hemoglobin that might indicate bleeding that can be unnoticed to the patient. Haemoglobin
long-term warfarin treatment needs monitoring of hemoglobin levels to detect any asymptomatic decrease in hemoglobin that might indicate bleeding that can be unnoticed to the patient.

Management - Supportive

Fact Explanation
Counsel the patient. Explain the importance of identifying symptoms and signs of complications(DVT) and the compliance with treatment.

Symptoms of DVT are acute onset leg swelling,erythema and calf pain (usually not associated with fever or local trauma.There may be acute onset varicose veins in some patients

Patient should be explained about the possibility of a pulmonary embolism and the high mortality rates.So acute onset chest pain, Dyspnoea, Haeoptysis should prompt urgent hospitalisation.

To minimize the above mentioned problems and prevent recurrence, adherence to treatment should be emphasized.
Counsel the patient.
Explain the importance of identifying symptoms and signs of complications(DVT) and the compliance with treatment.

Symptoms of DVT are acute onset leg swelling,erythema and calf pain (usually not associated with fever or local trauma.There may be acute onset varicose veins in some patients

Patient should be explained about the possibility of a pulmonary embolism and the high mortality rates.So acute onset chest pain, Dyspnoea, Haeoptysis should prompt urgent hospitalisation.

To minimize the above mentioned problems and prevent recurrence, adherence to treatment should be emphasized.
Explain the issues regarding the use of Warfarin Warfarin has some adverse effects
Ex1. Bleeding(GI, CNS,) so drugs such as NSAIDS should be avoided.

2.Drug interactions
Drugs such as Azoles,Sulpanomides,SNRIs and Antiarrhthmics(Amiaderone increase the action of Warfarin so dose adjustment is required.

Drugs such as anticonvulsents decrease the action of Warfarin.

Drugs such as Omeprazole, Cimetadine reduce the absorption so has to be substituted.

Avoid Warfarin in First trimester due to Teratogenicity.
Explain the issues regarding the use of Warfarin
Warfarin has some adverse effects
Ex1. Bleeding(GI, CNS,) so drugs such as NSAIDS should be avoided.

2.Drug interactions
Drugs such as Azoles,Sulpanomides,SNRIs and Antiarrhthmics(Amiaderone increase the action of Warfarin so dose adjustment is required.

Drugs such as anticonvulsents decrease the action of Warfarin.

Drugs such as Omeprazole, Cimetadine reduce the absorption so has to be substituted.

Avoid Warfarin in First trimester due to Teratogenicity.

Management - Specific

Fact Explanation
Venous Thromboembolism: initial treatment If there are no contraindications to heparin therapy such as active bleeding, allergy or documented HIT, unfractionated heparin, low molecular weight heparin or pentasaccharide (least 4 to 5 days) with warfarin overlap can be started as the initial therapy. Venous Thromboembolism: initial treatment
If there are no contraindications to heparin therapy such as active bleeding, allergy or documented HIT, unfractionated heparin, low molecular weight heparin or pentasaccharide (least 4 to 5 days) with warfarin overlap can be started as the initial therapy.
Venous Thromboembolism: long-term treatment Warfarin (or other vitamin K antagonists) administered with a target international normalized ratio (INR) of 2.0 to 3.0 is recommended In patients with APS and thrombocytopenia. . The duration of treatment is indefinite. With recurrent thrombosis, lifelong treatment is needed. Venous Thromboembolism: long-term treatment
Warfarin (or other vitamin K antagonists) administered with a target international normalized ratio (INR) of 2.0 to 3.0 is recommended In patients with APS and thrombocytopenia. . The duration of treatment is indefinite. With recurrent thrombosis, lifelong treatment is needed.
Management of arterial thrombosis. In a patient with stroke, aspirin is typically the first choice. Warfarin can be started in an ischemic stroke due to the risk of thrombosis. Myocardial infarction and peripheral arterial thromboembolism need long-term warfarin therapy. Management of arterial thrombosis.
In a patient with stroke, aspirin is typically the first choice. Warfarin can be started in an ischemic stroke due to the risk of thrombosis. Myocardial infarction and peripheral arterial thromboembolism need long-term warfarin therapy.
Antithrombotic recommendations during pregnancy Women with antiphospholipid syndrome, with no history of thrombosis low-dose aspirin with prophylactic unfractionated heparin or low molecular weight heparin, should be given in the antepartum period. One of the commonest obstetric complications of aPLS is pre-eclampsia. Antithrombotic recommendations during pregnancy
Women with antiphospholipid syndrome, with no history of thrombosis low-dose aspirin with prophylactic unfractionated heparin or low molecular weight heparin, should be given in the antepartum period. One of the commonest obstetric complications of aPLS is pre-eclampsia.
Treatment of associated thrombocytopenia Treatment should be initiated with overt bleeding or with increased risk of bleeding.
If platelet level is less than 20 to 30 × 109/L or if patient presents with bleeding, treatment can be considered. Changing the intensity of anticoagulant therapy in individual patient basis can be considered. Glucocorticoids, intravenous immune globulin (IVIgG), immunosuppressive agents (azathioprine, cyclophosphamide) are used.
Treatment of associated thrombocytopenia
Treatment should be initiated with overt bleeding or with increased risk of bleeding.
If platelet level is less than 20 to 30 × 109/L or if patient presents with bleeding, treatment can be considered. Changing the intensity of anticoagulant therapy in individual patient basis can be considered. Glucocorticoids, intravenous immune globulin (IVIgG), immunosuppressive agents (azathioprine, cyclophosphamide) are used.
Treatment of associated bleeding The antithrombotic agent needs to be discontinued first. The specific antidotes should be administered. i.e. Protamine sulfate for heparin, Vitamin K for warfarin. Administration of frozen plasma for heparins or warfarin, prothrombin complex concentrates for warfarin can be done in the acute management. Red cell transfusions for symptomatic anemia can be considered. If thrombocytopenia is detected, or if the patient is on aspirin, platelet transfusions may be given. Treatment of associated bleeding
The antithrombotic agent needs to be discontinued first. The specific antidotes should be administered. i.e. Protamine sulfate for heparin, Vitamin K for warfarin. Administration of frozen plasma for heparins or warfarin, prothrombin complex concentrates for warfarin can be done in the acute management. Red cell transfusions for symptomatic anemia can be considered. If thrombocytopenia is detected, or if the patient is on aspirin, platelet transfusions may be given.

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