Antiphospholipid Syndrome and Thrombosis

Abstract

Antiphospholipid antibodies [such as anticardiolipin antibodies (ACLA)] are strongly associated with thrombosis and appear to be the most common of the acquired blood protein defects causing thrombosis. Although the precise mechanism(s) whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagulable state remain unclear, several theories have been advanced. The most common thrombotic events associated with ACLA are deep vein thrombosis and pulmonary embolus (type I syndrome), coronary or peripheral artery thrombosis (type II syndrome) or cerebrovascular/retinal vessel thrombosis (type III syndrome), and occasionally patients present with mixtures (type IV syndrome). Type V patients are those with antiphospholipid antibodies and fetal wastage syndrome. It is as yet unclear how many seemingly normal individuals who may never develop manifestations of antiphospholipid syndrome (type VI) harbor asymptomatic antiphospholipid antibodies. The relative frequency of ACLA in association with arterial and venous thrombosis strongly suggests that these should be looked for in any individual with unexplained thrombosis; all three idiotypes (IgG, IgA, and IgM) should be assessed. Also, the type of syndrome (I through VI) should be defined, if possible, as this may dictate both type and duration of both immediate and long-term anticoagulant therapy. Unlike those with ACLA, patients with primary lupus anticoagulant thrombosis syndrome usually suffer venous thrombosis. Because the activated partial thromboplastin time (aPTT) is unreliable in patients with lupus anticoagulant (prolonged in only about 40 to 50% of patients) and is not usually prolonged in patients with anticardiolipin antibodies, definitive tests including ELISA for ACLA, the dRVVT for lupus anticoagulant, hexagonal phospholipid neutralization procedure, and B-2-GP-I (IgG, IgA, and IgM) should be immediately ordered when suspecting antiphospholipid syndrome or in individuals with otherwise unexplained thrombotic or thromboembolic events. If these are negative, in the appropriate clinical setting, subgroups should also be assessed. Finally, most patients with antiphospholipid thrombosis syndrome will fail warfarin therapy and, except for retinal vascular thrombosis, most will fail antiplatelet therapy, thus it is of major importance to make this diagnosis in order that patients can be treated with the most effective therapy for secondary prevention, low-molecular weight heparin (LMWH) or unfractionated heparin (UHF) in most instances.

A case of massive aortic thrombosis with catastrophic cerebrovascular embolization and infarction

“…Within the spectrum of the APS, anticardiolipin antibody syndrome is most commonly associated with arterial thrombosis, as opposed to left atrial, which is mainly related with venous thrombosis [3].…”

“…The most common site of arterial thrombosis in APS is central nervous system, with half of the cases resulting in strokes and transient ischemic attacks (TIAs) [3][4][5]. The major source of arterial systemic emboli is the heart, whereas systemic thrombi originating in the aorta are much less common.…”

"Possible Primary Antiphospholipid Syndrome" with Concurrent Diffuse Alveolar Hemorrhaging and Libman-Sacks Endocarditis Mimicking Catastrophic Antiphospholipid Syndrome

“…The best test for LA is the dRVVT, although no single test is 100% sensitive to all LA (7,8). Moreover, seronegative APS involving the typical clinical manifestations has recently been advocated, and aPL positivity is not always necessary for a diagnosis of APS (9).…”

Effects of Heparin Therapy on Hexagonal Lipid Neutralization Test

“…Evidence indicates that if the patient is taking heparin and the DRVVT is prolonged, the neutralization of the prolonged clotting time by platelet-derived phospholipid may not confirmatory, as large amounts of platelet-derived platelet factor 4 can inhibit the heparin effect [12,13]. This observation is particularly important since it demonstrates that UFH has a multiplex effect on plasma components which may not be entirely reflected by a correction in the TT with the addition of heparin neutralizing agents.…”