Disorders of Primary Haemostasis Flashcards
What is the source of platelets?
Megakaryocyte
What are the characteristics of platelets?
- platelet count → 1.5 - 4x10^(11)/L
- New platelets are larger and have a higher density than old platelets
- Circulation life span is 7-12 days
- Platelet survival is determine by peripheral platelet count of radiaoactively labelled platelets
- Removal of platelets is mainly by spleen > liver > BM = lymph nodes
What do the alpha granules of the platelet contain?
Coagulation proteins
1. Clotting factor V
2. Protein S
3. Plasminogen activatior inhibitor (PAI)
4. Series of adhesive plasma proteins: fibrinogen, fibronectin, VWF, vitronectin and thrombospondin
What do the delta granules of the platelet contain?
- Serotonin
- ADP
- ATP
- Phosphate
- Calcium
What is the difference between the shapes of a resting platelet vs an activated platelet?
Restign platelets are smooth and disc shaped, activated platelets have an irregular shape with many protruding pseudopodia
What is the function of platelet receptors?
- Hemostasis
- Inflammation
- Antimicrobial host defense
- Tumor growth
What are some examples of platelet receptors?
- Integrins
- Thrombin receptor
- ADP receptor
- Prostaglandin receptor
- Lipid and chemokine receptor
What are the receptors for collagen?
GPIa-IIa
GPIIb-IIIa
GPIV
What are the receptors for vWF?
GPIb-IX-V
GPIIb-IIIa
What are the receptors for fibrinogen?
GPIIb-IIIa
What are the receptors for fibronectin?
GPIc-IIa
GPIIb-IIIa
What are the receptors for thrombospondin?
Vitronectin receptor
GPIV
What happens after a signal on GPIb-IX-V?
Signal on GPIb-IX
- Transferred to the cytoplasm
- Activates GPIIb-IIIa
- Fibrinogen binding
What does fibrinogen depend on?
Calcium
What is atherothrombosis?
Characterized by sudden atherosclerotic plaque disruption (rupture/erosion) leading to platelet activation and thrombus formation.
Plaque rupture -> embolization -> microvascular obstruction
What is the link between thrombosis and inflammation?
Platelets modulate leukocyte adhesion at sites of inflammation by
1. Inducing a pro-inflammatory, pro-adhesive state in endothelial cells and leukocytes
2. Providing a bridge between the endothelium and leukocytes
What is are examples of acquired causes of platelet function defects?
- Uremia
- Myeloproliferative disorder
- Acute leukemia
- Antiplatelet Ab
- Liver disease
What are examples of inherited causes of platelet function defects?
- Platelet adhesion (BSS)
- Agonist receptors
- Signaling pathways
- Secretion
- Aggregation (Glanzmann)
- Platelet-coagulant protein interaction
What are the causes of thrombocytopenia? (EXAM)
- Reduced production
- Increased removal
What are the disorders of platelet secretion?
- Alpha granule storage disease (Gray Platelet Syndrome)
- rare congenital bleeding disorder caused by a reduction/absence of the platelet a-granules in blood platelets or of the proteins contained in these granules
- under microscopic analysis standard stain, no a-granules in platelets - Hermansky Pudlak syndrome
- dense granule deficiency in platelets
- decreased aggregation and secretion with multiple agonists
- defective pigmentation (albinism)
What is the treatment for Hermansky Pudlak syndrome?
- no cure, treatment for chronic hemorrhages only
- therapy with vit E and antidiretic Demopressin
- lifelong UV protection
- avoid anticoagulants like aspirin
What are the different quantitative platelet disorders?
- Idiopathic Thrombocytopenic Purpura (ITP)
- Disseminated Intravascualar Coagulation (DIC)
- Thrombotic Thrombocytopenic Purpura (TTP)
- Hemolytic Uremic Syndrome (HUS)
What is idiopathic thrombocytopenic purpura and what causes it?
Autoimmune disease where blood doesn’t clot normally and is caused by Ab against platelets
What is Disseminated Intravascualar Coagulation (DIC) triggered by? What are the clinical manifestations?
- triggered by inflammation, infection or cancer
- blood clots throughout body blocks small BV
- low platelet count, low fibrinogen level, high D-dimers (FGB degradation products)
- prolonged aPTT and PT
What is Thrombotic Thrombocytopenic Purpura (TTP) caused by? What is the pathophysiology? What is the treatment?
Caused by infections such as HIV
- extensive microscopic clots which can cause kidney, heart and brain damage
- lack of ADAMTS13 enzyme leads to OVERACTIVE BLOOD CLOTTING
Treatment:
- plasma transfusion to replace ADAMTS13
- NO PLATELET TRANSFUSION
What is Hemolytic Uremic Syndrome (HUS) caused by? What is the pathophysiology? clinical manifestations? What is the treatment?
Caused by infection such as E.coli species tht produces toxic substances (Shiga toxin)
acute kidney failure due to damage to the very small blood vessels of the kidney → destruction of RBC
Low RBC count (anemia), Low platelet count (thrombocytopenia)
Treatment: RBC & PLT transfusion
What are drugs that affect platelet function?
- Clopidogrel (ADP receptor agonist)
- Leads to an irreversible blockage of the ADP receptor on the platelet membrane - Aspirin (cyclooxygenase inhibitor)
- Anti-clotting effect and is used long term
- low doses to prevent MI, strokes, and blood clot
- low doses may be given immediately after MI to reduce the risk of another MI or death of cardiac tissue - Eptifibatide (GPII/III antagonist)
- antiplatelet drug tht selectivelyblocks the platelet GP-IIbIIIa receptor
