Disorders of Primary Hemostasis

What should the physician do to investigate abnormal bleeding?

• Take a complete history

• Order screening tests (PLT count, PT, APTT)

  • Order confirmatory tests (bleeding time/PFA, PLT aggregation, PLT function)

List hereditary disorders of the vasculature.

HEMP-O:

Hereditary Hemorrhagic Telangiectasia

Ehlers-Danlos Syndrome

Marfan Syndrome

Pseudoxanthoma Elasticum

Osteogenesis Imperfecta

List the acquired disorders of the vasculature.

SSHPP:

Senile Purpura

Scurvy

Henoch-Shonlein Purpura

Purpura secondary to dysproteinemias

Purpura secondary to vasculitis

List clinical reasons for increased platelet destruction.

Immunologic reasons

ITP

DIC/TTP/HUS

Heparin-Induced Thrombocytopenia

List clinical reasons for decreased platelet production.

M-WATCH:

May-Hegglin Anomaly

Wiskott-Aldrich Syndrome

Alport’s Syndrome

TAR Syndrome

Chediak-Higashi Anomaly

Hermansky-Pudlak Syndrome

What is the key problem in ITP?

Autoantibodies against platelet surface glycoproteins cause the platelets to be excessively removed by splenic macrophages.

What is the hallmark lab finding associated with ITP?

Isolated thrombocytopenia

What is the process that causes HIT?

Heparin mildly activates platelets, causing them to release PF 4.

Autoantibodies bind to the resulting heparin-PF 4 complexes, activating the platelet and causing thrombosis.

Platelets are consumed in the thrombi, causing thrombocytopenia.

What is the key problem in TTP?

Deficiency in ADAMSTS13 causes buildup of overly large vWF multimers in the blood. Platelets stick to them and form microthrombi that occlude capillaries major organs.

What are the clinical findings in TTP?

Neurologic symptoms

Heart failure

Pancreatic and adrenal gland damage

Abdominal pain

Widespread thrombosis

Malaise, weakness, fatigue, fever

Of DIC/TTP/HUS, which is associated with a hemoglobin level below 10.5 g/dL?

TTP

What is the key problem in HUS?

Shiga toxin (usually) damages vascular endothelial cells, triggering platelet adhesion and activation. Commonly seen in children <5 following gastroenteritis.

What are the clinical findings in HUS?

Acute onset of:

Renal failure

Hematuria

Bloody diarrhea, abdominal pain, vomiting

Bruising, petechiae

Fever

Hypertension

Of DIC/TTP/HUS, which is associated with abnormal coagulation studies?

DIC

What are the coagulation study results in DIC?

PT, APTT, and TT prolonged

FDP elevated

Fibrinogen decreased

Elevated SFMC or D-dimer

List causes of primary thrombocytosis.

MICE:

MDS 5q syndrome

Idiopathic refractory anemia

CML/PMF/PV
Essential thrombocythemia (ET)

List causes of reactive thrombocytosis.

Chronic inflammation

Surgery

Hemorrhage

IDA

Post-splenectomy

Transient causes (exercise, chidlbirth, etc.)

What are the three types of causes of thrombocytopenia?

Increased destruction

Decreased production

Abnormal sequestration

What are the two types of causes of thrombocytosis?

Primary

Reactive

What is the key problem in Bernard-Soulier Syndrome?

A defect in GPIb impairs binding to vWF. Causes impaired adhesion.

What are the hallmarks of Bernard-Soulier Syndrome?

Giant platelets + thrombocytopenia

Platelet aggregation studies for Bernard-Soulier Syndrome

ADP - Normal

Collagen - Normal

Epinephrine - Normal

Ristocetin - Abnormal

What is the key problem in von Willebrand Disease?

A qualitative or quantitative defect in vWF impairs adhesion. Can also impact Factor VIII.

What is the most common inherited bleeding disorder?

von Willebrand Disease

Platelet aggregation studies for VWD

ADP - Normal

Collagen - Normal

Epinephrine - Normal

Ristocetin - Abnormal

What is the key problem in Glanzmann’s thrombocytopenia?

A lack of GPIIb/IIIa prevents platelets from aggregating.

Platelet aggregation studies for Glanzmann’s thrombocytopenia

ADP - No response

Collagen - No response

Epinephrine - No response

Ristocetin - Normal

What is the key problem in dense storage pool disease?

Platelets lack the ability to effectively release their dense granule contents. This impairs amplification of the platelet response.

Wha tis the platelet morphology in dense storage pool disease?

Platelets appear normal on the PBS, but lack dense granules on EM

Platelet aggregation studies for dense storage pool disease

ADP - Decreased response

Epinephrine - No second wave

Low [Collagen] - Decreased response

Ristocetin - Slight reduction

What is the key problem in gray platelet syndrome?

Absent or markedly reduced alpha granules; impairs secretion and platelet function.

Which syndrome is associated with mild bleeding following surgical procedures?

Gray platelet syndrome

Which disorder is associated with possible thrombocytopenia?

Gray platelet syndrome

What is the platelet morphology associated with gray platelet syndrome?

Platelets lack granulomeres and appear grey/pale

Platelet aggregation studies in gray platelet syndrome

ADP - Normal

Collagen - Normal

Epinephrine - Normal

Ristocetin - Normal

Platelet aggregation studies in ASA intake

ADP - decreased response/no second wave

Collagen - decreased response/no second wave

Epinephrine - No aggregation

Ristocetin - Normal

What effect do NSAIDs have in the body?

They reversibly inhibit COX-1.