Antiphospholipid syndrome This is a disorder characterized by recurrent venous or arterial thrombosis and/or recurrent fetal losses typical laboratory

abnormalities such as elevated levels of antibodies directed against membrane phospholipids their associated plasma proteins, predominantly b2 glycoprotein I (apolipoprotein H), clotting factors

It was formerly known as Lupus anticoagulant (LA) syndrome It may be primary or secondary (associated with SLE or other autoimmune disorder)

Pathophysiology: The series of events following production of autoantibodies to platelet phospholipids or clotting factors leads to hypercoagulability and the resultant recurrent thrombosis can affect virtually any organ system

Mortality/Morbidity: APS may contribute to an increased incidence of thrombotic (or embolic) cerebrovascular accidents (CVA) especially in younger individuals. myocardial infarctions Cardiac valvular disease (???) Recurrent pulmonary emboli or thrombosis with resultant pulmonary hypertension. multiple organ infarctions spontaneous fetal loss

Epidemiology Race: it has a higher prevalence of SLE occurs in black and Hispanic populations. Sex: it is commoner in females particularly in secondary APS. Age: APS occurs more commonly in young-to-middleaged adults;

History:

The American College of Rheumatology has proposed that at least 1 clinical criterion and 1 laboratory criterion must be present for a patient to be diagnosed as having APS. The clinical criteria includes One or more episodes of vascular thrombosis in any vessel in any organ eg CHD, MI, DVT, PI, PE etc Frequent miscarriages or premature births Other clinical features may include entities like Nonthrombotic neurologic symptoms, such as -migraine headaches -transverse myelitis -dementia (rare) History of heart murmur or cardiac valvular vegetations Hematologic abnormalities, such as thrombocytopenia or hemolytic anemia Livedo reticularis Unexplained adrenal insufficiency Avascular necrosis of bone in the absence of other risk factors Pulmonary hypertension -chorea -seizures

-Guillain-Barr syndrome

Physical: -Cutaneous -Livedo reticularis -Leg ulcers -Superficial thrombophlebitis -Painful purpura

-Splinter hemorrhages -Venous thrombosis -Leg swelling (DVT) -Ascites (Budd-Chiari syndrome)

-Tachypnea (pulmonary embolism) -Generalized edema (renal vein thrombosis) -Abnormal results on fundoscopic examination (retinal vein thrombosis) -Arterial thrombosis -CVA -Digital ulcers

-Gangrene of distal extremities -Signs of myocardial infarction (raised JVP and reducing pulse pressure) -Heart murmur, frequently aortic or mitral insufficiency (Libman-Sacks endocarditis) -Abnormal results on funduscopic examination (retinal artery occlusion)

Causes: APS is an autoimmune disorder of unknown cause. May be associated numerous autoimmune or rheumatic diseases, infections, and drugs e.g. Rheumatic diseases -SLE Autoimmune diseases -Autoimmune thrombocytopenic purpura (ITP) -Autoimmune hemolytic anemia (AIHA) -Psoriatic arthritis -Systemic sclerosis -Mixed connective tissue disease -Polymyalgia rheumatica or giant cell arteritis -Behet syndrome Infections -Syphilis -Malaria -Hepatitis C -HIV -Sjgren syndrome -Rheumatoid arthritis

-Bacterial septicemia

-Human T-cell lymphotrophic virus type 1 (HTLV-1) Drugs -Cardiac - Procainamide -quinidine -hydralazine -Neuroleptic or psychiatric - Phenytoin -chlorpromazine -propranolol

-Other - Interferon-alpha, quinine, amoxicillin A genetic predisposition exists. It has been associated with certain HLA genes such as DRw53, DR7 (mostly people of Hispanic origin) and DR4 (mostly whites).

DIFFERENTIALS Disseminated Intravascular Coagulation Infective Endocarditis Thrombotic Thrombocytopenic Purpura Hypercoagulable state Malignancy,

Malignancy, oral contraceptive use, homocystinemia, antithrombin III deficiency, protein C or S deficiency, factor V Leiden mutation, prothrombin A20210 Atherosclerotic vascular disease, including multiple cholesterol emboli syndrome Systemic necrotizing vasculitis

Investigations Antiphospholipid antibodies or abnormalities in phospholipid-dependent tests of coagulation. Anti-b2 glycoprotein I antibodies Activated partial thromboplastin time (aPTT) Dilute Russell viper venom time (DRVVT) False-positive serologic test for syphilis (STS) due to cardiolipin Complete blood count (thrombocytopenia, Coombs positive hemolytic anemia) LAs are directed against plasma coagulation proteins. In vitro, this interaction results in the paradoxical prolongation of clotting assays, such as the aPTT, the kaolin clotting time, and the DRVVT. The presence of LA (and not a clotting factor deficiency) is confirmed by mixing of normal platelet-poor plasma with the patients plasma. If no LA is present, this mix will correct the prolonged clotting time. FBC may reveal -hemolytic anemia and this has been associated with the presence of IgM anticardiolipin antibodies or -thrombocytopenia which is associated with a paradoxical high risk for thrombosis or an increased risk of bleeding. ANA (may not always imply coexisting SLE) In addition to the clinical criteria above, at least 1 of the following laboratory criteria are necessary for the classification of APS: Presence of anticardiolipin antibody (IgG or IgM) in blood on 2 or more occasions at least 6 weeks apart Presence of LA on 2 or more occasions at least 6 weeks apart and detected by any of the above described methods

Imaging Studies: CT scanning or magnetic resonance imaging (MRI) of the brain (CVA) or CT scanning of the abdomen (Budd-Chiari syndrome). Doppler ultrasound studies are recommended for suspected DVT. Two-dimensional (2-D) echocardiography may demonstrate vegetations or valvular insufficiency; aortic or mitral insufficiency is the most common valvular defect found with Libman-Sacks endocarditis.

TREATMENT Medical Care: Patients with APS may be managed on outpatient or inpatient basis depending on the severity of the disease Prophylactic therapy Eliminate other risk factors, such as oral contraceptives, smoking, hypertension, or hyperlipidemia. Antiplatelet drugs e.g. low-dose aspirin, ticlopidine and clopidogrel Consider the use hydroxychloroquine in a patient with SLE. Postthrombosis: -Full anticoagulation with i.v. heparin is followed by warfarin. Treatment with intensive anticoagulation and plasmapheresis, corticosteroids and IVIG may be used.

Surgical Care: Recurrent DVT may necessitate placement of an inferior vena cava filter.