Platelets

Question 1

Where are platelets made and from what pre-cursor?

Answer 1

• Made in Bone marrow
• from Megakaryocytes

Question 2

What is the hormonal stimulus for platelet production?

Answer 2

Thrombopoeitin

Question 3

3 Steps of Platelet Plug Formation (Details)

Answer 3

• Adhesion
  
  • Platelets stick to vWF in subendothelium
  • vWF sticks to GP Ib/IX on platelet
    
    • also sticks to collagen in vessel wall
• Aggregation
  
  • Platelets stick to eachother via fibrinogen bridges
  • Fibrinogen binds to platelet receptor GP IIb/IIIa
  • activated by:
    
    • Thrombin
    • TxA2
    • Collagen
    • ADP
    • Epinephrine
    • Serotonin
• Secretion
  
  • platelets release granular secretions that promote clots
    *

Question 4

Petichiae & Purpura are signs of what regarding platelets?

Answer 4

Plateley hypoperfusion

Question 5

Basis of pseudothrombocytopenia

Answer 5

• Some patients have a factor that makes their blot clot when exposed to the EDTA in test tubes
• If not considered, reported platelet count will be much lower than in vivo count
• NO CLINICAL SEQUELLAE

Question 6

Symptoms of pseudothrombocytopenia

Answer 6

• Mucocutaneous bleeding (“oozing and bruising”)
• **NO JOINT/MUSCULAR BLEEDS **
  
  • these are more like hemophilia
• Classic primary hemostasis defects

Question 7

3 Categories of Thrombocytopenis DDx

Answer 7

• Underproduction
• Peripheral Destruction
• Splenic sequestration

Question 8

Platet Undreproduction Characteristics

Answer 8

• Hallmark: Decreased megakaryocytes in bone marrow
• Could be due to
  
  • Marrow failure
  • Marrow infiltration
  • Marrow toxins

Question 9

Peripheral Destruction Mechanisms

Answer 9

• DIC
• TTP
• HUS

Question 10

DIffuse Intravascular Coagulation (DIC)

Answer 10

• Abnormal Coag. activation, thrombin generation, clotting factor consumption , platelet destruction
• Lab
  
  • Increased PT
  • Decreased platelets
  • Decreased fibrinogen
  • Increased fibrin degeneration products (D-Dimers)
  • Schistocytes
• Etiologies
  
  • Gram (-) sepsis
  • Burns
  • OB complications
  • Leukemias
  • Shock
  • Venom
• Treatment
  
  • Platelet transfusion
  • clotting factors
  • fibrinogen

Question 11

Thrombotic Thrombocytopenic Purpura (TTP)

Answer 11

• Abnormal platelet activation, vWF deposition, RBC and platelet destruction
• Diagnosis - THE PENTAD
  
  • MAHA - MUST BE PRESENT
  • Schistocytes - MUST BE PRESENT
  • Low platelets
  • Fever
  • Neurologic manifestations
  • Renal Manifestations
  • “My Parents Never Forget Rent…but My Parents MUST BE PRESENT”
• Etiologies
  
  • Antibody against ADAMTS-13, which processes vWF
  • Drugs
    
    • Quinine
    • Cyclosporine
    • tacrolimus
  • increased chance with pregnancy or AIDS
• Treatment
  
  • Plasma exchange (PLEX)
  • Corticosteroids (will only work with PLEX)
  • NO PLATELET TRANSFUSIONS
  • Splenectomy
  • RItuximab

Question 12

Hemolytic Uremic Syndrome (HUS)

Answer 12

• Overlaps with TTP
• Fewer Neuro, more renal symptoms
• Precipitated by diarrheal symptoms (E. Coli/Shigella)
• see more in children
• not as good response to PLEX

Question 13

Immune Mediated Thrombocytopenia

Answer 13

• Antibodies binding to platelets via Fc receptors (Ig mediated) and destroying them via RE System macrophages
• NO DIAGNOSTIC TEST like coombs for hemolysis
• Same 3 mechanisms for action for drug induced thrombocytopenia as for drug induced hemolysis
  
  • Innocent bystander
  • Hapten mechanism
  • True Immune Mechanism
• Drugs that can cause this
  
  • Beta lactam antibiotics
  • Sulfa Drugs
  • Quinine/quinidine
  • Heparin

Question 14

Why is Heparin dangerous?

Answer 14

• Can cause paradoxical thrombosis
• starts off as decreased platelet count…if this happens STOP HEPARIN IMMEDIATELY

Question 15

Immune mediated/Idiopathic Thrombocytopenic Purpura (ITP)

Answer 15

• Diagnosis of exclusion
• Should see megakaryocytes in bone marrow
• Spontaneous remission in children
• Adults need treatment
  
  • Corticosteroids
  • IVIg if more severe
  • Splenectomy - 2nd line
  • Rituximab - 3rd line

Question 16

Usefulness of platelet transfusions in TTP, ITP, Splenic sequestration, Platelet hypofunction

Answer 16

• ITP - not helpful unless actively bleeding (bc platelet survival is very short)
• TTP - contraindicated (fuel to fire)
• Splenic Sequestration - transfused platelets will go to spleen, so not that helpful unless for acute bleeding
• Platelet hypofunction - will get transfusion if platelet number is <10k
• can always use prophalactically to increase plt count to treat acute bleeding

Question 17

Primary vs Secondary Thrombocytosis

Answer 17

• Primary - myeloproliferative diseases
  
  • Essential Thrombocytopenia
  • Polycythemia Vera
• Secondary - Reactive
  
  • Inflammation, bleeding, decreased Fe
  • no abnormal clotting
  • no special therapy - treat underlying cause

Question 18

How do you diagnose qualitative platelet disorders?

Answer 18

• look for Increased bleeding time
• Use Platelet Function Assay (PFA)
• PT/PPT/TCT should be normal

Question 19

Differential Diagnosis for Qualitative Platelet Disorders

Answer 19

• Congenital
  
  • Glanzmann’s Thromboaesthenia
  • Bernard-Soulier
• Aquired
  
  • Uremia
  • Drugs
    
    • Asprin (ASA)
    • NSAIDs
    • Myeloproliferative Diseases