Antiphospholipid syndrome (or antiphospholipid antibody syndrome) is a disorder of coagulation which causes thrombosis in both arteries and veins, as well as recurrent miscarriage. It is due to the autoimmune production of antibodies against cell membrane constituents. It is occasionally referred to as Hughes’ syndrome after the rheumatologist Dr Graham R.V. Hughes (St Thomas’ Hospital, London, UK).

A very rare form is the catastrophic antiphospholipid syndrome, in which there is rapid organ dysfunction and arterial hypertension. It carries a high mortality.

Signs and symptoms
The presence of antiphospholipid antibodies (APLAs) is suggested by thrombosis (arterial or venous) and recurrent miscarriage (especially in the second trimester, but often earlier). Other common findings, although not part of the classification, are thrombocytopenia (low platelet count) and livedo reticularis (a skin condition). Many patients report headaches.

APLAs are present in the blood in the context of a number of diseases, most notably systemic lupus erythematosus (SLE). One can only speak of antiphospolipid syndrome when there are no other symptoms of one of these diseases (e.g. arthritis suggestive of SLE). A number of patients with the syndrome (about 10%) will eventually develop SLE, but most never get signs of this disease.

The diagnosis is often entertained in cases of thrombophilia (recurrent thrombosis) or recurrent miscarriage. Tests that are often performed at the same time are a full blood count, liver enzyme studies and renal function studies.

Thrombophilia screening can consist of:

Screening coagulation studies: APTT, PT and TT.
Further studies for Factor V Leiden variant and the prothrombin mutation, Factor VIII levels, MTHFR mutation.
Levels of protein C, free and total protein S, Factor VIII, antithrombin, plasminogen, tissue plasminogen activator (TPA) and plasminogen activator inhibitor-1 (PAI-1)
Antiphospholipid syndrome is tested for in the laboratory by using a minimum of two coagulation tests that are phospholipid sensitive. The patient on initial screening will typically have been found to have a prolonged APTT that does not correct in a 80:20 mixture with normal human plasma (50:50 mixes with normal plasma are insensitive to all but the highest antibody levels). The APTT (plus 80:20 mix), dilute Russell viper venom time (DRVVT), the kaolin clotting time (KCT) or dilute thromboplastin time {TDT/DTT) are the prinicipal tests used for the detection of lupus anticoagulant. A further antibody can be detected using an enzyme-linked immunosorbant assay (ELISA) immunological test, which screens for the presence of antibodies to anticardiolipin.

Low platelet count and positivity for antibodies against β2-glycoprotein or phosphotidylserine may also be observed in a positive diagnosis.

The diagnosis is made in case of a clinical event (thrombosis or recurrent miscarriage after 10 weeks gestation) and repeated positive tests of lupus anticoagulant and/or anticardiolipin antibodies performed 6-8 weeks apart. Repeat testing is necessary due to the naturally occurring presence of transient high levels of antiphospholipid antibodies following infection and inflammation. Other antibodies, although implicated, are not yet considered relevant for diagnosis.

Antiphospholipid syndrome is an autoimmune disease, in which antibodies react against anionic phospholipids on cell membranes. Being an autoimmune disease, it is more common in women than in men. The exact cause is not known, but activation of the system of coagulation is evident.

Often, this disease is treated by giving aspirin to inhibit platelet activation, and/or warfarin as an anticoagulant. The goal of the prophylactic treatment is to maintain the patient’s INR between 2.0-3.0. It is not usually done in patients who have not had any thrombotic symptoms. During pregnancy, heparin is used instead of warfarin because of warfarin’s teratogenicity.

Women with recurrent miscarriage are often advised to take aspirin and to start heparin (or low molecular weight heparin) treatment after missing a period. This is the most effective treatment at the moment.

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