Autoimmune Diseases Affecting Hemostasis: A Narrative Review

Abstract

Hemostasis reflects a homeostatic mechanism that aims to balance out pro-coagulant and anti-coagulant forces to maintain blood flow within the circulation. Simplistically, a relative excess of procoagulant forces can lead to thrombosis, and a relative excess of anticoagulant forces can lead to bleeding. There are a wide variety of congenital disorders associated with bleeding or thrombosis. In addition, there exist a vast array of autoimmune diseases that can also lead to either bleeding or thrombosis. For example, autoantibodies generated against clotting factors can lead to bleeding, of which acquired hemophilia A is the most common. As another example, autoimmune-mediated antibodies against phospholipids can generate a prothrombotic milieu in a condition known as antiphospholipid (antibody) syndrome (APS). Moreover, there exist various autoimmunity promoting environments that can lead to a variety of antibodies that affect hemostasis. Coronavirus disease 2019 (COVID-19) represents perhaps the contemporary example of such a state, with potential development of a kaleidoscope of such antibodies that primarily drive thrombosis, but may also lead to bleeding on rarer occasions. We provide here a narrative review to discuss the interaction between various autoimmune diseases and hemostasis.

Keywords: COVID-19; acquired hemophilia; antiphospholipid (antibody) syndrome (APS); autoimmune disease; bleeding; hemostasis; heparin induced thrombotic thrombocytopenia; immune thrombocytopenia; immune thrombotic thrombocytopenia; lupus anticoagulant; thrombosis; vaccine induced (immune) thrombotic thrombocytopenia.

Figure 1

Hemostasis can be considered as reflecting a balance of procoagulant and anticoagulant forces. (A) In normal individuals, these forces are in balance, and this acts to prevent overt bleeding or thrombosis. (B) In some pathological states, a relative reduction in procoagulant forces or an excess of anticoagulant forces, can lead to a hemostasis disbalance and bleeding. (C) In some pathological states, an excess of procoagulants forces, or a relative reduction in anticoagulant forces, can lead to a hemostasis disbalance and thrombosis.

Figure 2

Virchow’s triad. Thrombosis can occur due to the disruption of any of the three components listed.

Figure 3

The historical cascade model of hemostasis reflects a series of protease-led activation of subsequent factors in the cascade, and closely reflects the routine laboratory tests we use to broadly assess coagulation. The ‘contact factor pathway’ (also historically known as the intrinsic pathway of coagulation) essentially matches the activated partial thromboplastin time (APTT) test, the ‘tissue factor pathway’ (also historically known as the extrinsic pathway of coagulation) essentially matches the prothrombin time (PT) test. Both converge into a so-called common pathway, which ultimately leads to generation of thrombin (activated factor II), and conversion of the most abundant coagulation plasma protein (soluble) fibrinogen to (insoluble) fibrin. A series of natural anticoagulants (protein C [PC], protein S [PS] and antithrombin [AT] help to control the coagulation process.

Figure 4

The cell based or platelet-driven model of hemostasis reflects the incorporation of platelets and other components of primary hemostasis (e.g., plasma and platelet derived VWF) and the secondary elements of hemostasis (i.e., clotting factors) to provide a composite hemostasis process. Platelets provide both the building blocks to the formation of the platelet plug (or thrombus) as well as the assembly point for secondary hemostasis pathways. Platelets contain various granules which release their cargo upon platelet activation; this cargo comprises procoagulant material such as factor V, fibrinogen, and VWF.