Hematology Ch. 17

Defects of Plasma Clotting Factors

What are plasma clotting factors?

inactive enzymes that circulate in plasma that are activated by injury

What are hemophilias?

• a group of disorders in which particular clotting factors are decreased

• two types: hemophilia A and hemophilia B

What is Hemophilia A?

• a factor VIII deficiency

  • VIII is the only factor not produced in the liver

  • factor VIII forms a complex with vWF, which transports it to circulation

• symptoms:

  • circumcisional bleeds, umbilical cord bleeds

  • challenges in crawling, walking, and running

  • bleeding in the GI tract, kidneys, gums, and hematomas

  • muscle or joint bleeds

  • intracranial bleeds

  • longer bleeding times

What is the lab diagnosis and treatment of Hemophilia A?

• lab diagnosis

  • normal PT, but increased PTT

  • vWF is normal

  • single factor assays are performed to assess the activity of a clotting factor

    • PTT test

    • patient plasma is mixed with a prepared factor-deficient plasma

    • if PTT remains abnormal, the patient is missing the same factor as the prepared plasma

    • if PTT is normal, the patient has the factor that the prepared plasma is lacking

• treatment

  • gene therapy

    • factor VIII is inserted into a virus vector that enters the body and produces normal amounts of VIII

What are Factor VIII inhibitors?

• autoantibodies created against factor VIII that are time and temperature-dependent

• capable of neutralizing the coagulation portion of factor VIII

• develops in 15%-20% of individuals with hemophilia A

• treatment is difficult

  • patients either have an infusion of factor VIII or a substitute

How are clotting factors measured?

• by their percent activity

  • in normal hemostasis, 30% of all clotting factors must be available for use

  • in hemophilia: less than 1% is severe, 1%-5% is moderate, and 6%-24% is mild

• AND by their function in coagulation tests

What is hemophilia B (Christmas Disease)?

• a factor IX deficiency

• makes up 10% of all hemophilia cases

• same inheritance, symptoms, diagnosis, and complications as Hemophilia A

• marked by a prolonged PTT and decreased factor assay activity

• treatment

  • factor IX concentrates or prothrombin complex factors

What are some congenital factor deficiencies with bleeding manifestations?

• Factors II, V, VII, and X

• causes

  • skin and mucous membrane bleeding

  • occasional joint bleeding

• treatment

  • prothrombin complex concentrate

Describe the following factor deficiencies: Factor XI, Factor XII, Fletcher factor, and Fitzgerald factor

• XI

  • bleeding is unlikely unless trauma or surgery occurs

• XII

  • prolonged PTT, they don’t bleed, but are more prone to thrombosis

• Fletcher

  • prolonged PTT, causes thrombotic events (MIs or pulmonary embolisms)

• Fitzgerald

  • causes deep vein thrombosis or pulmonary embolism

Describe Factor XIII deficiency

• causes poor wound healing, keloid formation (raised scars after trauma), spontaneous abortion, and recurrent hematomas

• normal PT and PTT

• screening is done with a urea test

  • measures the stability and firmness of a clot

  • if there is a deficiency, the clot will be stringy and loose

What are some secondary conditions that can cause decreased number of clotting factors?

• liver disease

  • bleeding patients are treated with fresh frozen plasma containing clotting factors

• renal disease

  • patients are cautioned against taking aspirin and platelet inhibitors

• autoimmune diseases

• these conditions result in excessive bleeding, due to low clotting factors

List 5 conditions that affect factor production and function

• alcoholic cirrhosis

• biliary cancer

• congenital liver defects

• obstructive liver disease

• hepatitis

What is vitamin K essential for in coagulation, how can you get the vitamin in your diet, and what population is usually deficient?

• vitamin K is a fat soluble vitamin that is required for Factors II, VII, IX, and X to work properly

• diet

  • leafy greens, veggies, fish, soybeans, olive oil, gut bacterial also produces some

• newborns are usually deficient and therefore get a vitamin K shot

What causes vitamin K deficiency, how do lab tests show this deficiency, and how is it treated?

• causes

  • dietary deficiency, long-term antibiotic use, chronic diarrhea, liver disease, or warfarin

• lab tests show

  • elevated PT and PTT

  • factor assays of specific vitamin K-dependent factors reveal decreased activity

• treatment

  • oral vitamin K or infusion, blood product infusion

Which test is abnormal in a factor X deficiency?

PT and PTT

A fatal bleed in a patient with hemophilia involves:

intracranial bleeding

Which disorder is the most prevalent inherited bleeding disorder?

von Willebrand Disease

A prolonged PTT is corrected with factor VIII-deficient plasma but not with factor IX-deficient plasma. What factor is deficient?

Factor IX