Catastrophic Antiphospholipid Syndrome

Abstract

Unlike classic APS, CAPS causes multiple microthrombosis due to an increased inflammatory response, known as a "thrombotic storm". CAPS typically develops after infection, trauma, or surgery and begins with the following symptoms: fever, thrombocytopenia, muscle weakness, visual and cognitive disturbances, abdominal pain, renal failure, and disseminated intravascular coagulation. Although the presence of antiphospholipid antibodies in the blood is one of the diagnostic criteria, the level of these antibodies can fluctuate significantly, which complicates the diagnostic process and can lead to erroneous interpretation of rapidly developing symptoms. Triple therapy is often used to treat CAPS, which includes the use of anticoagulants, plasmapheresis, and high doses of glucocorticosteroids and, in some cases, additional intravenous immunoglobulins. The use of LMWH is recommended as the drug of choice due to its anti-inflammatory and anticoagulant properties. CAPS is a multifactorial disease that requires not only an interdisciplinary approach but also highly qualified medical care, adequate and timely diagnosis, and appropriate prevention in the context of relapse or occurrence of the disease. Improved new clinical protocols and education of medical personnel regarding CAPS can significantly improve the therapeutic approach and reduce mortality rates.

Keywords: antiphospholipid antibodies; antiphospholipid syndrome; catastrophic antiphospholipid syndrome; complications of pregnancy.

Figure 1

Effects of APLA on the complement system, inflammation, and vascular tone. β2GP1—β2-glycoprotein I, ApoER2—apolipoprotein E2 receptor, DAB2—Disabled-2, PP2A—Protein phosphatase 2A, eNOS—nitric oxide synthase, sENG—soluble Endoglin, TLR-4—toll-like receptor 4, TLT-8—toll-like receptor 8. APLA reduces eNOS activity via ApoER2 interaction. Decreased NO production results in impaired vasodilatation and endothelial dysfunction. APLA activates TLR and inflammasome pathways, triggering the secretion of inflammatory cytokines and chemokines. APLA activates complement on the cell surface, leading to the coagulation activation and cell damage by C5b-9 deposition. Black arrow down—decrease; black arrow up—increase.

Figure 2

Effects of APLA on the coagulation cascade and fibrinolysis. PC—protein C. PS—protein S. aPC—activated protein C. TF—tissue factor. ATIII—antithrombin III. PolyP—anionic polyphosphates. TM—thrombomodulin. APLA prevents thrombin inactivation by inhibiting antithrombin III. APLA may interfere with the components of protein C activation pathway and inhibit its anticoagulant effect, leading to an increased risk of thrombosis. APLA inhibits tPA-mediated conversion of plasminogen to plasmin, leading to dysregulation and suppression of fibrinolysis.

Figure 3

CAPS: the “two-hit” theory. APLA—antiphospholipid antibody, β2GPI—β2-glycoprotein I. Acute precipitating factors as a 2nd hit lead to systemic inflammation and endothelial damage. Massive cytokine release, NET formation and coagulation activation result in microthrombosis and CAPS.

Figure 4

The mechanisms of hemostasis disorders in severe SARS-CoV-2 and CAPS. CAPS—catastrophic APS, NETs—neutrophil extracellular traps, SIRS—systemic inflammatory response syndrome, DIC—disseminated intravascular coagulation. Black arrow down—decrease; black arrow up—increase.