Bleeding Disorders I

Question 1

Define the following terms

• Purpura
• Petechia
• Ecchymosis
• Hematoma
• Hemarthrosis

Answer 1

• Purpura : bleeding within skin or mucous membranes
• Petechia : pin point bleeding of skin or mucous membranes (a type of purpura)
• Ecchymosis : large confluent area of bleeding within skin, larger than petechiae (a type of purpura)
• Hematoma : a collection of blood in an organ, space, or tissue
• Hemarthrosis : bleeding into the joint space

Question 2

What is the clinical significance of petechiae and skeletal muscle hematoma/hemarthrosis?

Answer 2

Petechia are seen in vascular and platelet disorders whereas hematoma/hemarthrosis are seen in coagulation disorder

Question 3

Explain hereditary hemorrhagic telangiectasia.

Answer 3

Autosomal dominant AkaOsler-Weber-Rendu syndrome.

• Inherited disorder of blood vessels, weak venules lead to recurrent bleeding. Caused by mutation in endoglin gene or activin- receptor-like kinase 1 gene
• Thickened smooth muscle layer and absent elastin fibers in venule wall
• Findings: branching skin lesions (telangiectasias), recurrent epistaxis, skin discolorations, arteriovenous malformations (AVMs), GI bleeding, hematuria.

Question 4

Explain Henoch-Schonlein Purpura.

Answer 4

Henoch-Schonlein Purpura

• Most common childhood systemic vasculitis.
• Acquired disorder, often follows URI, viral infection or drugs. Classic triad:
• Skin: palpable purpura on buttocks/legs
• Arthralgias
• GI: abdominal pain
• Vasculitis 2° to IgA immune complex deposition.
• Associated with IgA nephropathy (Berger disease).
• Fibrinoid necrosis of vessel walls.

Question 5

What is a common feature of platelet disorders?

Answer 5

All of them result in an increase in bleeding time and a decrease in platelet count - thrombocytopenia

Question 6

Explain immune thrombocytopenia purpura.

Answer 6

• Anti-Gp2b-3a antibodiesŽ, leads to splenic macrophage consumption of platelet-antibody complex.
• Commonly due to viral illness. Can also be due to SLE or lymphoma
• Excessive bleeding, skin, muscosa, there can be even intracranial bleeding.
• Increased megakaryocytes on bone marrow biopsy.
• Treatment: steroids, IVIG, Rituximab, splenectomy (for refractory ITP).

Question 7

Explain thrombotic thrombocytopenic purpura.

Answer 7

• Inhibition or deficiency of ADAMTS 13 (vWF metalloprotease), leads to decrease in degradation of vWF multimers.
• Pathogenesis: increased large vWF multimersŽ platelet, leads to increased plateletadhesionŽ, aggregation and thrombosis. Labs:
• Schistocytes,
• Increased serum LDH
• Hyaline microthrombi are seen within the arterioles and capillaries (this is the cause of renal failure in thisdisease) Classic pentad:
• Micrangiopathic hemolytic anemia
• Thrombocytopenia
• Fever
• Neurologic deficits
• Renal failure
• Treatment: plasmapheresis, Rituximab, steroids.

Question 8

Explain hemolytic uremic syndrome.

Answer 8

• Characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure.
• Typical HUS is seen in children, accompanied by diarrhea and commonly caused by Shiga toxin-producing E coli (STEC) (eg, O157:H7).
• HUS in adults does not present with diarrhea; STEC infection not required. Same spectrum as thrombotic thrombocytopenic purpura (TTP), with a similar clinical presentation and same initial treatment of plasmapheresis.
• Hyaline mircothrombi
• Schistocytosis
• Elevated serum LDH
• Thrombocytopenia NO neurologic symptoms!

Question 9

What are qualitative platelet disorders that are associated with platelet receptor defects?

Answer 9

Qualitative Platelet Disorders –Inherited Platelet Receptor DefectsBernard-Soulier Syndrome
* GP Ib/V/IX deficiency
* Defective platelet adhesion
* Diagnosed by platelet aggregation testing
* No platelet aggregation response to ristocetin
Glanzmann thrombasthenia
* GP IIb/IIIa deficiency
* Defective platelet aggregation
* Diagnosed by platelet aggregation testing
* No platelet aggregation response to epinephrine, ADP, collagen, arachidonic acid, thrombin
* Normal platelet aggregation response to ristocetin

Question 10

What are qualitative platelet disorders that are associated with platelet granule defects?

Answer 10

Qualitative Platelet Disorders –Inherited Platelet Granule DefectsAlpha Storage Pool Disease
* Deficiency of alpha granules (protein-rich)
* Defective platelet aggregation
* Bleeding is mild to moderate in severity
* Diagnosed by electron microscopy
Delta Storage Pool Disease
* Decreased or defective delta granules (ADP-rich)
* Defective platelet aggregation
* Bleeding is mild to moderate in severity
* Diagnosed by platelet aggregation testing