Hematology Ch 16

Quantitative and Qualitative Platelet Disorders

What are the two types of platelet disorders?

• Qualitative

  • Less common

  • Problems with platelet function.

  • Assess via platelet aggregation studies and bleeding time.

• Quantitative

  • More common

  • Includes various "thrombocytopenias" (assess via platelet count)

  • Either decreased production or increased destruction of platelets.

Qualitative Platelet Disorders

• Inherited

• impaired platelet function, usually bleeding time is prolonged.

• Intrinsic defect of platelets

• May be a disorder of adhesion and platelet release OR a storage pool defect.

• Disorders of Adhesion

  • Von Willebrand's Disease (vWD)

  • Bernard Soulier Syndrome (BSS)

  • Glanzmann's Thrombasthenia (GT)

vWD (Von Willebrand's Disease)

• Disorder of adhesion.

• Qualitative or quantitative defect in Von Willebrand's Factor (vWF).

  • a large glycoprotein used for platelet adhesion

• Symptoms:

  • Heavy menses (menorrhagia)

  • excessive bleeding after dental procedures

  • epistaxis (nose bleeds)

  • ecchymoses (bruising)

  • easy bleeding

vWD Lab Tests

•PLT count: usually normal

•PTT: increased most of the time

•Bleeding time: prolonged

GT (Glanzmann's Thrombasthenia)

• Disorder of adhesion.

• Autosomal recessive disorder

• Abnormality of GPIIb and IIIa

  • important for aggregation

• Variable bleeding patterns: Umbilical cord bleeding, gingival bleeding, purpura, prolonged bleeding from minor cuts

• symptoms

  • normal platelet count and morphology, but abnormal platelet aggregation

• treatment

  • oral contraceptives (for menorrhagia)

  • epsilon aminocaproic acid (used as a topical thrombin-inducing agent)

GT Tests

•Bleeding time: prolonged

•Platelet count: normal

•Normal platelet morphology

•Abnormal aggregation

• all aggregating agents are present except for ristocetin

BSS (Bernard Soulier Syndrome)

• Disorder of adhesion.

• Rare adhesion defect of platelets involving GP Ib-IX receptor for vWF.

  • Ib-IX complex is site for: thrombin binding, regulating platelet shape, and regulating reactivity

  • inhibits platelets from sticking to collagen to create a platelet plug

• symptoms

  • Epistaxis, Gingival bleeding, Menorrhagia, Purpura, Thrombocytopenia with giant platelets

• treatment

  • platelet transfusion

What are some preanalytical factors that can cause thrombocytopenia?

• blood not being filled to the line in light blue tubes

  • wrong ratio (supposed to be 9:1)

• patient may have platelet satelitism

What are some causes of thrombocytopenia related to decreased production?

• bone marrow issues

  • lack of platelets (aplasia) or megakaryocytes

  • leukemia

  • megaloblastic conditions (causes pancytopenia)

• cytotoxic agents or chemotherapy

• bacterial infections

• viral infections

  • CMV, EBV, HCV, HIV, varicella, or rubella

How can altered distribution of platelets lead to thrombocytopenia?

• the spleen holds 1/3 of all platelets

• an enlarged spleen can cause blood to pool, withholding platelets from circulation

  • caused by myeloproliferative disorders, extramedullary hematopoiesis, and hemolytic anemias

• splenectomy can cause thrombotic conditions due to increased platelets in circulation

Drug induced immune thrombocytopenia (DIT)

• reduced platelet count

• can be dangerous and cause significant bleeding

• drugs that cause it:

  • quinines, NSAIDs, heparin, anticonvulsants, sulfanomides, diuretics, and amoxicilin

• two things cause it:

  • ingestion results in anti-drug antibody formation that binds to platelets and eventually causes the removal of platelets from circulation (low PLT count)

  • drug combines with larger carrier proteins forming an antigen that triggers an antibody response, results in platelet destruction

Thrombocytopenia

•Low platelet count

•PLT <150 K/uL

•Bleeding signs: Gingival, nose (epistaxis), extensive bruising (ecchymoses), pinpoint hemorrhages (petechiae).

•60-100 K/uL will bleed in surgery

•30-50 K/uL will have petechiae in the absence of trauma.

•5 K/uL has a high risk of CNS hemorrhage.

•The first thing to do when PLT# is low is check the smear to confirm!!!

ITP (Idiopathic (Immune) Thrombocytopenic Purpura)

• autoantibody (IgG) destroys platelets, leading to thrombocytopenia

  • Autoantibody (IgG) against GP IIb/IIIA or GP Ib-IX.

• Two types

  • Chronic

    • Platelet count 30−60

    • Age 20−50 years.

    • Lasts months to years.

  • Acute

    • Platelet count as low as 20

    • Age usually 2−6 years.

    • Often caused by virus.

    • Lasts 2−6 weeks.

TTP (Thrombotic Thrombocytopenic Purpura)

• acute and unpreditable thrombocytopenia

• Platelet count <20

• PT and PTT normal

• excessive platelet adhesion and aggregation

• Smear shows schistocytes resulting from clot formation.

• Severe hemolytic anemia called microangiopathic hemolytic anemia.

HUS (Hemolytic Uremic Syndrome)

• Thrombocytopenia

• presence of nitrogenous waste products in blood (uremia)

• Usually affects age 6 months−4 years

• Mimics TTP except renal damage is more severe.

• Renal damage caused by toxin produced by E. coli O157:H7 or Shigella.

• Patients may present with:

  • Bloody diarrhea

  • Microangiopathic hemolytic anemia

  • Thrombocytopenia

  • Renal failure

Thrombocytosis

• Platelet count is >450

• Primary thrombocytosis

  • caused by myeloproliferative disorders

  • increased number, but impaired function

• Secondary thrombocytosis

  • seen in acute and chronic blood loss (spleen throws out more platelets), chronic inflammatory disease, post-splenectomy (No place to store platelets anymore), and iron deficiency anemia

• Platelet function is normal.

What are platelet release defects?

• inherited disorders

• characterized by abnormal secondary phases of platelet aggregation and granule release

• associated with postoperative bleeding, menorrhagia, and easy bruising

• platelet count is normal

What are 2 causes of acquired defects of platelet function?

• drug-related defects

  • aspirin can inhibit production of platelet aggregator thromboxane A2

    • can also be used to prevent strokes, MIs, or other CV events

• secondary disorders

  • renal disease, uremia, and multiple myeloma or Waldenstrom

How can skin, collagen, or blood vessel abnormalities cause platelet dysfunction?

• can cause mucosal bleeding, purpura, petechia, ecchymosis, or telangiectasia

• PLT count and function is normal

What is purpura?

small, reddish-purple spots on the skin, caused by small blood vessels leaking

nose bleeding, deep bruising, and gum bleeding are usually manifestations of which type of coagulation disorder?

platelet defects