Info

🌱 來自: Huppert’s Notes

Coagulation Disorders

•   Definition: Elevated prothrombin time (PT) and/or partial thromboplastin time (PTT) with normal platelet count and bleeding time

•   Differential diagnosis for coagulation disorders:

-   Prolonged PT, normal PTT: Factor VII deficiency or inhibitor, DIC, liver disease, vitamin K deficiency, warfarin

-   Normal PT, prolonged PTT: Deficiency of factors VIII, IX, or XI, Von Willebrand Disease (vWD, if severe, which can result in low levels of factor VIII), heparin exposure

-   Prolonged PT and PTT: Deficiency of factors V, X, II, or fibrinogen, severe liver disease, DIC, vitamin K deficiency, heparin overdose. If low fibrinogen is causing PT/PTT elevation, correcting fibrinogen should correct the PT/PTT as well.

-   Normal PT and PTT: Platelet dysfunction (acquired or congenital), vWD (if mild and factor VIII level not too low), scurvy, Ehlers-Danlos, hereditary hemorrhagic telangiectasia, deficiency of factor XII

-   Note: Since there is some crosstalk between the PT and PTT pathways, disease states that elevate one of these coagulation markers may elevate the other somewhat as well.

Hemophilia A/B

•   Pathophysiology: X-linked recessive disorder (more common in males)

-   Hemophilia A = factor VIII deficiency (more common)

-   Hemophilia B = factor IX deficiency

•   Clinical features: Cannot distinguish hemophilia A and B clinically. Common symptoms: 1) Hemarthrosis – bleeding into muscles/joints, 2) Intracranial or retroperitoneal hematoma, 3) Hematuria, hemospermia.

•   Diagnosis: ↑PTT, normal PT. Factor activity assays (VIII, IX) are abnormal. Normal bleeding time (unlike vWF). Mixing studies correct PTT (as opposed to disorders due to inhibitors, such as lupus anticoagulant, that do not correct with mixing).

•   Treatment:

-   Replace missing factor. Note that over time, patients can form autoantibodies to factor.

-   Hemophilia A only: DDAVP can be used to treat mild disease (leads to a 2–4-fold factor VIII increase)

Vitamin K deficiency

•   Pathophysiology: Vitamin K comes from diet (leafy green vegetables) and gut flora. Taking antibiotics can kill gut flora and decrease vitamin K. Can also have malabsorption of vitamin K with IBD or other malabsorptive conditions.

•   Clinical features: Increased bleeding; initially ↑PT (factor VII has the shortest half-life) then ↑PTT

•   Treatment: Vitamin K replacement (10 mg PO/SQ ×3 days). If severe bleeding: IV vitamin K or FFP.

Coagulopathy of liver disease

•   Pathophysiology: Liver failure → 1) ↓Synthesis of clotting factors, 2) Cholestasis = ↓vitamin K absorption, 3) Hypersplenism, portal hypertension → sequestration of platelets → thrombocytopenia

•   Clinical features: Abnormal bleeding (e.g., GI bleed), ↑PT ↑PTT

-   To distinguish between liver failure, DIC, and vitamin K/warfarin overdose, check factors V, VII, VIII:

•   DIC = all low

•   Liver failure = normal factor VIII (synthesized by all endothelial cells, not just the liver)

•   Vitamin K/warfarin overdose = normal factor V (not vitamin K-dependent)

•   Treatment: FFP, try giving vitamin K in case the patient is vitamin K deficient, platelet transfusions if thrombocytopenic, cryoprecipitate if hypofibrinogenemic