Coagulation Disorders

Coagulation Cascade

To understand the coagulation disorders, an understanding of the coagulation cascade is necessary.
The coagulation cascade consists of an extrinsic and intrinsic pathway both of which end in a common pathway. The extrinsic pathway begins when damaged tissue releases thromboplastin. Thromboplastin activates factor VII and the activated factor VII then activates factors IX and X.

The intrinsic pathway begins when exposure to subendothelial collagen or exposure to high molecular weight kininogen (HMWK) activates factor XII which is also known as Hageman factor. The activated factor XII then activates factor XI which goes on to activate factor X. Activated factor IX needs to be in a complex with activated factor VIII, platelet factor 3 (PF3) and calcium. Calcium is needed to bind the activated coagulation factor.

The common pathway begins with activated factor X which can be arrived at by either the intrinsic or extrinsic pathways. Activated factor X forms a complex with factor V, PF3, and calcium. This complex is called the prothrombin complex and its job is to cleave prothrombin (factor II) into thrombin. Thrombin then breaks down fibrinogen (factor I) into fibrin monomers and fibrinopeptides. Thrombin also activates factor XIII. The fibrin monomers aggregate to form soluble fibrin which is stabilized into cross-link formation by activated factor XIIIa.

Note: activated factor XII also activates plasminogen which produces plasmin and kininogen which produces kallikrein and bradykinin.

Classification

Coagulation disorders can be divided in to acquired and hereditary disorders. Acquired disorders include vitamin K deficiency and disseminated intravascular coagulation (DIC). Hereditary disorders include the hemophilias and von Willebrand disease.

Coagulation factor deficiencies vs Platelet disorders

Coagulation disorders can also be grouped based on whether the disorder affects coagulation factors or platelets. We can figure out if bleeding in a patient is due to a coagulation factor or a platelet disorder by looking at the pattern of bleeding. With factor deficiencies, bleeding occurs in deeper tissues, for example, bleeding in joints (hemarthroses), bleeding in deep muscles, and retroperitoneal bleeding. When there is poor platelet quality or low platelet count, the bleeding is more mucosal. Platelet deficiencies result in bleeding from the nose (epistaxis), easy bruising, blood in the urine (hematuria), heavy menstrual bleeding (menorrhagia), etc.

Laboratory values can also help us distinguish whether bleeding is factor related or platelet related.
Bleeding time (BT) assesses platelet function. PT and aPTT assess the coagulation system. Activated partial thromboplastin time (aPTT) assesses the intrinsic pathway and prothrombin time (PT) assesses the extrinsic pathway.

For example, factor VIII deficiency affects the intrinsic pathway and we expect to see a prolonged aPTT. While factor VII deficiency affects the extrinsic pathway and we expect to see a prolonged PT.