19, 20 - Hereditary + Acquired bleeding disorders

When we see isolated prolonged aPTT, why does it matter whether the patient is bleeding vs. asymptomatic/thrombotic?

Isolated prolonged aPTT indicates an issue with the intrinsic pathway:

• If with bleeding: A more essential factor is missing, like VIII, IX, or XI, all useful for the propagation phase of the cell-based model

• Asymptomatic/thrombosis: A less essential clot forming factor is deficient: XII, prekallikrein, HMWK

Isolated prolonged PT usually indicates deficiency of what factor?

Factor VII

Hemophilia

• Types and what they are

• What kind of disease

• Mechanism

• Clinical/lab signs(4 + 2)

• Hemophilia A(More common and a deficiency in factor VIII) and hemophilia B(a deficiency in factor IX)

• A X-linked recessive disease

• Factor VIII and IX are both involved in creating the tenase complex that creates factor Xa, crucial in making lots of thrombin, meaning that we will be unable to do proper hemostasis

• Hemarthrosis on and off, muscle hematomas, delayed bleeding, deep ecchymoses, isolated prolonged aPTT(Because the intrinsic pathway is affected) successful mixing test

Giving 1 unit/kg of factor VIII and IX raises the level in plasma by how much?

Factor VIII: 2 U/dL

Factor IX: 1 U/dL

What are the half-lives of factor VIII and IX?

Factor VIII: 12 hours

Factor IX: 24 hours

vWF main functions

1. Bridge platelets and collagen in primary hemostasis

2. Binds factor VIII in the bloodstream

What is ADAMTS13, and why is it important?

• An enzyme that cuts vWF multimers into proper size

What are the types of vWF defects?

Type 1: Quantitative defect, usually asymptomatic until the body is put under real bleeding stress like surgery

Type 2A: Qualitative effect, vWF multimers are cut down too small and leads to primary hemostasis like symptoms

Type 2N: Qualitative effect, vWF can’t bind factor VIII, so it’s cleared too fast, looks like hemophilia A

Type 3: Most severe, no vWF at all → primary and secondary hemostasis symptoms

Which blood type has lower vWF than other types?

• Type O

What are the key vWF tests, and why?

vWF:Ag(antigen) test, measures total quantity + vWF:RCo(Ristocetin cofactor assay) measures activity, or how well it functions

• Important to do both because we can then tell if the issue is due to a type 1 or 2 vWF disease

What is a key recognition pattern for a vWF disease?

• Primary hemostasis error signs but with normal platelet count

ITP

• Stands for

• What is it and what is the mechanism

• Diagnostic threshold(one number)

• Main causes(2)

• Symptoms

• Lab tests

• Immune thrombocytopenia

• An autoimmune attack on our platelets. B cells produce autoantibodies vs platelets causing spleen destruction, but also inhibiting megakaryocytes, while T cells also target platelets due to T-regs being relatively deficient to cytotoxic T cells

• <100k platelets

• Primary(idiopathic) and secondary, such as SLE

• Symptoms of primary hemostasis with other values in CBC normal aside from platelets

• CBC and PBS, anti HIV-HCV, HBsAg(to rule out things like chronic viral infections that can cause secondary ITP)

DIC

• Stands for

• What is it and what is the mechanism

• Main causes(3)

• Symptoms(5)

• Disseminated Intravascular Coagulation

• It is a condition where clotting and coagulation occurs all over the body; this leads to fibrin forming everywhere which can cause organ failure if blood flow is blocked, but since there’s fibrin, fibrinolysis happens too, leading to high D-Dimer. This leads to platelets and clotting factors all being used up.

• Causes are usually infections causing a massive inflammatory response(like monocytes that have lots of TF), or malignancies and major trauma

• Bleeding, thrombocytopenia, prolonged PT/aPTT, and MAHA blood picture(Microangiopathic hemolytic anemia) which has schistocytes(RBCs fragmented due to getting sliced as they flow past fibrin), polychromasia, D-dimer elevation

Vitamin K role in normal hemostasis

• Helps the liver produce factors II, VII, IX, X as a cofactor

How does warfarin affect vitamin K?

• Inhibits vitamin K function

Vitamin K deficiency

• What is it and what is the mechanism?

• Impact on PT and aPTT

• Causes(3)

• Symptoms(2)

• Inactivate vitamin K impacts the production of factors II, VII, IX, and X

• Both will be prolonged because the common pathway is impacted(II, X) but PT will be affected more because factor VII has the shortest half life, while factor IX’s “team”, factor VIII and XI are still normal

• Poor dietary intake/malabsorption, antibiotics that kill vitamin D producing cut bacteria, Warfarin

• Prolonged PT and aPTT(PT more), secondary hemostasis signs

What factor is spared in cirrhosis?

• Factor VIII

Why is PT and aPTT impacted differently in different stages of cirrhosis?

1. Early liver impairment: Only PT affected because factor VII is the first to go

2. Advanced: Both are prolonged because now we have factor I, II, V, VII, IX, and X deficiency

Cirrhosis

• Mechanism

• Causes(2)

• Key symptoms/lab results(7)

• Chronic liver damage impacts synthesis of clotting factors(II, V, VII, IX, X, fibrinogen) → secondary hemostasis defect while portal hypertension causes splenomegaly and leads to thrombocytopenia

• Alcoholism, viral hepatitis, etc.

• Thrombocytopenia, secondary and primary hemostatic effects, low albumin, high AST/ALT, jaundice, spider nevi, ascites

APDE

• Stands for

• Mechanism

• Key symptoms/lab pattern(2)

• Acquired Platelet Dysfunction with Eosinophilia

• High eosinophils toxic granules apparently damages platelet function

• Primary hemostasis defects with eosinophilia with normal platelet count, normal PT aPTT.

VICC

• Stands for

• Cause and mechanism

• Symptoms/lab findings(5)

• Venom induced consumption coagulopathy

• Procoagulant toxins in snake venom (mainly vipers, also Australasian elapids) directly activate multiple steps of the coagulation cascade at once (Factor X, Factor V, prothrombin, fibrinogen), causing a rapid, uncontrolled burst of real clot formation right after the bite. This quickly consumes the body's fibrinogen, prothrombin, and Factors V/X faster than the liver can replace them — so by the time the patient is tested, reserves are depleted and they can no longer clot normally → bleeding. Same consumption logic as DIC, but from one clear trigger (the bite) and without DIC's systemic microthrombi/organ failure — faster onset, faster resolution, lower mortality.

• Local swelling at bite, systemic bleeding(Like at gums or even GI or intracranial), high D-dimer, prolonged PT/APTT, low fibrinogen(depleted)