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A Review of Coagulation Disorders for the Physician Assistant Exam

On the Physician Assistant Exam (PANCE), there are some blood-related questions concerning coagulation problems and their evaluation and management. To prepare for the test, focus on platelets’ coagulation and factor disorders.

Many things can affect platelets’ ability to stick together. Medications, including antiplatelet agents, hinder clotting. Commonly prescribed medications like aspirin, antiplatelet agents like ticlopidine (Ticlid), clopidogrel (Plavix), and nonsteroidals like ibuprofen (Motrin) also can affect platelet clotting.

One major medical condition that can affect how platelets work is uremia. The uremic toxins in advanced kidney disease can affect the ability of platelets to clump. In that case, the treatment is dialysis.

The administration of clotting factors depends on which coagulation problem you’re dealing with. Fresh frozen plasma (FFP) is part of the blood that’s frozen and kept after a blood transfusion; it contains all the coagulation factors. Compared to FFP, cryoprecipitate (which is also frozen) contains Factor VIII, fibrinogen, vWF, and Factor XIII.

Von Willebrand disease: Mucous membrane bleeding

Von Willebrand disease (vWD) is an extremely common hereditary coagulation disorder that’s characterized by mucous membrane bleeding. It’s inherited in an autosomal dominant fashion. There are several different types of von Willebrand disease, but for the purposes of the test, concern yourself only with Type I. Here are the key points about this condition:

  • Clinical presentations can include minor or major bleeding. Minor cases include excessive bleeding after a trauma or dental surgery. Major bleeding includes recurrent nosebleeds (epistaxis), GI bleeding, and bleeding from the GU tract.

  • Important labs include an abnormal bleeding time, reduced plasma von Willebrand’s factor (vWF) levels, and low Factor VIII activity levels. Understand that physiologically, von Willebrand disease is linked to Factor III. This link comes up again in regard to hemophilia A.

  • Treatments involve giving Factor VIII concentrates or desmopressin. This can raise the vWF level; however, these treatments are indicated only for certain forms of vWF.

Hemophilia

Hemophilia comes in various types, but for test-taking purposes, focus on hemophilia A.Hemophilia A, the most common type, is an X-linked inherited disease. Here are some key points about hemophilia A:

  • One can have significant bleeding into almost any body cavity; common places include the joints (hemarthroses), the head, the gastrointestinal tract, and the genitourinary tract (hematuria). If not treated, bleeding can persist from days to weeks.

  • Hemophilia A causes significant bleeding due to a deficiency in Factor VIII, so to diagnose hemophilia A, you need to order a specific assay for Factor VIII. Labwise, the PTT level is prolonged.

  • Do not use any antiplatelet agents.

  • The gold standard is transfusion with Factor VIII concentrate that is purified to reduce the incidence of infection.

Christmas disease is important to differentiate from other causes of hemophilia because the treatment differs. Christmas disease involves a deficiency of Factor IX. Clinically, Factor IX deficiency can present in a similar way to Factor VIII, so make sure you know which factor deficiency you’re dealing with. To diagnose hemophilia B, you order a specific assay for Factor IX. The treatment involves administering a purified or recombinant Factor IX concentrate.

Concentrates of Factor VIII and Factor IX can cause activation of the clotting cascade and promote a clotting problem. An alternative solution is to give fresh frozen plasma to the person with hemophilia who is unable to receive the Factor concentrates.

Vitamin K: The clotting pathway

Vitamin K is a fat-soluble vitamin that’s important in the clotting pathway. Working in the medical field, we’ve come across patients on warfarin (Coumadin) whose PT/INR levels (which measure the extrinsic pathway of coagulation) were scary high. If you recall, warfarin works on a vitamin K–dependent pathway.

Here are some key points concerning vitamin K deficiencies:

  • Common causes of low vitamin K levels include advanced liver disease, antibiotics, poor nutrition, and malabsorptive processes.

  • The PT/INR is elevated in people with vitamin K deficiency.

  • Coagulation and vitamin K synthesis can be significantly compromised in a cirrhotic liver. If liver disease is advanced, the liver enzymes can be normal because not enough functioning hepatic cells are left to increase the liver enzymes.

  • Vitamin K can be given orally or subcutaneously. Vitamin K supplements may not be effective in liver disease because the liver may not be able to process the vitamin K.

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