Platelet Disorders

Question 1

platelets - basics

Answer 1

*disc shaped, 2-4 micrometers, anuclear
*blue/gray with reddish/purple granules
*normal counts 150k-400k
*circulate for 7-9 days
*2/3 in circulating blood, 1/3 in spleen
*precursor = megakaryocyte

Question 2

thrombopoietin (TPO) & platelet production

Answer 2

*a glycoprotein that binds to its receptor on platelets and megakaryocytes
*produced at a constant rate by the liver
*inverse relationship b/w serum TPO levels and platelet mass
*TPO concentration regulated by the total mass of platelets/megakaryocytes available to bind and degrade the protein

Question 3

components of a platelet

Answer 3

*open canalicular system
*lysosome
*mitochondria
*alpha granules: fibrinogen, von Willebrand factor, platelet factor 4
*dense granules: ADP, serotonin

Question 4

events of primary hemostasis

Answer 4

1. following blood vessel injury, platelets adhere to the exposed subendothelial connective tissues
2. under the influence of shear stress, platelets move along the surface of vessels until the platelet engages sub-endothelial collagen (and/or vWF)

Question 5

platelet functions

Answer 5

1. initial function - formation of mechanical plugs during the normal hemostatic response to vascular injury
2. local release of potent paracrine vasoconstrictors to decrease blood flow to the injured area
3. catalysis of reactions of the soluble coagulation cascade leading to fibrin clot formation (secondary formation)
4. initiation of the tissue repair process
5. regulation of local inflammation

Question 6

thrombocytopenia

Answer 6

*defined as platelet count < 150,000 microliters
*consequences:
-bleeding following surgery or trauma with PLT counts < 50k
-spontaneous hemorrhage with platelet counts < 10k
-transfusion threshold

Question 7

examples of failure of platelet production causing thrombocytopenia

Answer 7

1. selective megakaryocyte depression
   -rare congenital defects
   -drugs, chemicals, viral infections
2. part of general bone marrow failure
   -cytotoxic drugs (chemo)
   -radiation
   -marrow infiltration
   -HIV infection

Question 8

examples of consumptive thrombocytopenias

Answer 8

1. immune
   -autoimmune/idiopathic (ITP)
   -infections: HIV, malaria
   -drug-induced
   -HIT
   -post-transfusional purpura
2. disseminated intravascular coagulation (DIC)
3. thrombotic thrombocytopenia purpura (TTP)

Question 9

immune thrombocytopenia (ITP) - defined

Answer 9

*an acquired form of thrombocytopenia in which patients produce antibodies that bind to their own platelets, erroneously marking them for destruction in the spleen
*results in reduced platelet count
*can present as a chronic or acute disease

Question 10

immune thrombocytopenia (ITP) - pathogenesis

Answer 10

*development of antibodies (usually IgG) against one’s own platelets → bind to platelet membrane glycoproteins IIb/IIa → macrophages in the spleen degrade antibody-coated platelets → reduced platelet numbers

*common causes of ITP include: mostly idiopathic; viral infections, antiviral vaccines, autoimmune diseases, etc

Question 11

immune thrombocytopenic purpura (ITP) - acute

Answer 11

*abrupt onset of bleeding, petechiae, mucosal bleeding in a previously healthy person
*may follow an infection, usually a nonspecific URI or GI virus
*majority recover without treatment
*giant platelets appear

Question 12

diagnosis & treatment of immune thrombocytopenic purpura (ITP)

Answer 12

*dx: dx of exclusion; must be an ISOLATED thrombocytopenia

1. target the immune system: steroids, splenectomy, immune globulin, rituximab, splenic tyrosine kinase inhibitors
2. increase platelet production: thrombopoietin receptor agonists stimulate megakaryocytes

Question 13

heparin induced thrombocytopenia (HIT) - overview

Answer 13

*despite thrombocytopenia, one of the most thrombotic conditions -> platelet ACTIVATING
*IgG Abs directed agsint heparin-platelet factor 4 complex
*suspect if platelet count falls to < 100,000 5-15 days after heparin therapy started
**venous, arterial, and microvascular thrombosis threatens life and limb
*risks: any patient on heparin

Question 14

thrombotic thrombocytopenic purpura (TTP) - clinical presentation

Answer 14

*devastating disorder; fatal if untreated
*clinical “pentad”:
1. fever
2. anemia
3. thrombocytopenia
4. renal dysfunction
5. neurologic deficits
*blood film: schistocytes + few platelets

Question 15

thrombotic thrombocytopenic purpura (TTP) - pathophysiology

Answer 15

*the absence or impairment of ADAMTS13 (vWF cleaving enzyme) allows for the persistence of the ultralarge “sticky” forms of vWF, which trap platelets and cause thrombi in vessels
*leading to end-organ damage and the appearance of the pentad of clinical features

Question 16

contraindications to platelet transfusion

Answer 16

TTP (thrombotic thrombocytopenic purpura) and HIT (heparin induced thrombocytopenia)

Question 17

pseudothrombocytopenia

Answer 17

*due to in vitro agglutination of platelets (platelets low in test tube because the platelets clump in there, not in body)