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75 Cards in this Set
- Front
- Back
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Platelets
Morphology |
Disc shaped, 2-4um, anuclear
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Platelets
Histology |
Blue gray on Wright's stain with reddish-purple granules
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Platelets
Life span |
Circulate for 7-9 days
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Platelets
Body Distribution |
2/3rds in blood
1/3 in spleen |
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Platelets
Normal Counts |
Normal counts 150-450K/uL
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Thrombopoietin (TPO) is a ...
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- glycoprotein that binds to its receptor on platelets and megakaryocytes
- it acts at all stages of differentiation (stem cell to platelet) |
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What regulates the concentration of TPO in the blood?
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- TPO concentration regulated by the total mass of PLTs/megakaryocytes available to bind and degrade the protein
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Thrombopoietin is produced...
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- produced at a constant rate by the liver
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What is the relationship between platelets and TPO?
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- inverse relationship between free serum TPO levels and platelet mass
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What functions are the platelet granule contents responsible for?
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1. platelet adhesion
2. aggregation 3. templating for the coagulation cascade 4. vessel repair and recannulation |
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Why is the dense tubular system of the platelets important?
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allow for invagination of the membrane
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Contents of Alpha Granules
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1. Fibrinogen
2. von Willebrand factor 3. Platelet factor 4 4. Platelet derived growth factor 5. Beta-throboglobulin Factor V 6. Factor XI 7. Protein S 6. |
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Contents of Dense Bodies
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1. ADP
2. ATP 3. Calcium 4. Serotonin |
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Why is Serotonin (from the dense bodies of platelets) important?
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vasoconstriction
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Why is ADP (from the dense bodies of platelets) important?
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activates neighboring platelets
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What are the components of hemostasis?
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1. Blood vessels --> vasoconstriction
2. Platelets --> platelet adhesion 3. Soluble factors --> fibrin formation |
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What are the 5 functions of platelets?
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1. Main function – formation of mechanical plugs during the normal haemostatic response to vascular injury
2. Local release of vasoconstrictors to decrease blood flow to the injured area 3. Catalysis of reactions of the soluble coagulation cascade leading to fibrin clot formation 4. Initiation of the tissue repair process 5. Regulation of local inflammation |
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What are the series of functional events that lead to thrombus (clot) formation?
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adhesion
spreading aggregation |
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Platelet Adhesion
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platelets roll and cling to non-platelet surfaces
> this is reversible, seal endothelial gaps, requires VWF in arterioles |
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Platelet Aggregation
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platelets cling to each other
>irreversible, platelet plugs form, secretion of all platelet contetns, requires FIBRINOGEN |
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Platelet Secretion
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platelets discharge the contents of their granules
>irreversible, occurs during aggregation, essential to coagulation |
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Where do platelets travel in a blood vessel?
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platelets travel near to the endothelium
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Glycoprotein 1b
(Gp Ib) |
is a glycoprotein on the surface of an activated platelet that beinds to von Wilebrand factor
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Where is von Wilebrand factor?
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on the collagen of the injured endothelium
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Bernard-Soulier Disease
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- defect, absence or decrease in the GpIb, factor IX, and Factor V (for class purposes just GpIb)
- an autosomal recessive disorder |
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Events of Primary Hemostasis
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1. blood vessel injury
2. platelets adhere to the exposed subendothelial connective tissues 3. Under the influence of shear stress, platelets engage collagen (Adhesion) 4. platelets extrude long pseudopods which enhance interaction between adjacent platelets (Aggregation) 5. Platelet activation is then achieved by glycoprotein IIb/IIIa binding fibrinogen to produce platelet aggregation. |
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Where does aspirin act?
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Cyclo-oxygenase
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What is cyclo-oxygenase responsible for?
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arachidonic acid --> endoperoxides (PGG2 and PGH2)
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Thromboxane
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- powerful platelet activator
- produced in platelets, then released from platelet to activate other platelets |
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Glanzmann Thrombasthenia
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a hemorrhagic dz characterized by normal or prolonged bleeding time, normal coagulation time, defective clot retraction, and normal platelet count, but morphologic or functional abnormality of platelets;
- caused by DEFECT IN PLATELET MEMBRANE GLYCOPROTEIN IIb-IIIa COMPLEX - autosomal recessive inheritance |
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What does GpIIbIIIa do?
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- must be activated by signal transduction
- activated glycoprotein interacts with calcium and fibrinogen for platelet aggregation (cross links) |
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List inducers of aggregation
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thrombin
TXA2 ADP Collagen PAF |
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List reversible inhibitors of aggregation
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Adenosine
NO (increase cGMP) PGI2 Dipyridamole (increase cGMP, increase adenosine) |
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List irreversible inhibitors of aggregation
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Ticlopidine (ADP)
Clopidogrell (ADP) Aspirin (COX) Plavix |
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Where is clopidogrels site of action?
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at ADP where it allows aggregation
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Thrombocytopenia
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platelet count <150,000/ul
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What are consequences of thrombocytopenia?
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Bleeding following surgery or trauma with PLT counts < 50K
Spontaneous hemorrhage with PLT counts < 10K |
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Transfusion threshold for Thrombocytopenia
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give transfusion to cancer patients if they have less than 10,000/ uL platelets
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Sites of Bleeding with Thrombocytopenia
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Cutaneous
Mucosal CNS |
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Cutaneous Sites of Bleeding with Thrombocytopenia
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petechiae
purpura ecchymosis venipuncture sites |
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Mucosal Sites of Bleeding with Thrombocytopenia
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epistaxis
menorrhagia hemorrhagic bullae in mouth GI bleeding |
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What type of bleeding do you see with thrombocytopenia?
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oozing not gushing (because there is a defect in forming a plug)
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Petechiae
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pinpoint brusing
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Purpura
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1 cm bruising
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menorrhagia
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Excessively prolonged or profuse menses
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Causes of Thrombocytopenia
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Failure of platelet production
Increased consumption of platelets Abnormal distribution of platelets Dilutional Loss |
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Failure of Platelet Production
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Selective megakaryocyte depression
Part of general bone marrow failure |
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Selective megakaryocyte depression
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Rare congenital defects
Drugs, chemicals, viral infections |
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Part of general bone marrow failure
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Cytotoxic drugs
Radiation Marrow infiltration HIV infection |
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May-Hegglin anomaly
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Rare inherited form of thrombocytopenia
Platelet and neutrophil production problem Neutrophils have purple inclusions |
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Thrombocytopenia and Absent Radii Syndrome
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disease in which children are born without radii and with thrombocytopenia
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Gray Platelet Syndrome
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platelets lack contents of dense granules
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Increased consumption of platelets
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Disseminated intravascular coagulation (DIC)
Thrombotic thrombocytopenic purpura (TTP) Immune |
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Immune related causes of increased consumption of platelets
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Autoimmune/idiopathic (ITP)
Infections: HIV, malaria Drug-induced Heparin (HIT) Post-transfusional purpura |
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Acute Immune Thrombocytopenic Purpura
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-Abrupt onset of bruising, petechiae, mucosal bleeding in a previously healthy person
-May follow an infection, usually a nonspecific URI or GI virus -Majority recover without treatment - most often does not require treatment |
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Chronic Immune Thrombocytopenic Purpura
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less responsive to therapy
-adults are more likely to have chronic ITP |
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Giant Platelet
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Morphology:
-Platelet larger than a normal red cell. Found in: (bone marrow problems) -Increased platelet turnover -Myeloproliferative disorders -Myelodysplastic disorders |
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Pathogenesis of ITP
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- A Disease of Accelerated Platelet Destruction and Suboptimal Platelet Production
- Production of antiplatelet Abs - After attachment, Fc region of Ab is detected by macrophages in the spleen and platelets are removed - megakaryocytes also undergo apoptosis when Abs bind |
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Treatment of ITP
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Target the Immune System
Increase Platelet Production |
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How do you Increase Platelet Production?
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Thrombopoietin Receptor Agonists stimulate megakaryocytes
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How do you target the immune system in treatment of ITP?
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1. Steroids - decrease interaction between T and B cells to down regulate immunoglobulins
2. Splenectomy 3. IVIG (immune globulin) |
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Drugs producing thrombocytopenia
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Ethanol
Heparin Phenytoin Quinine Quinidine Sulfas |
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Why should you ask thrombocytopenic patients if they drink tonic water?
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Because tonic water has quinine in it
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Heparin Induced Thrombocytopenia
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- IgG Abs directed against heparin-platelet factor 4 complex (from alpha granules)
- Suspect if platelet count falls to <100,000/ul or <50% of baseline value 5 to 15 days after heparin therapy is started - Feared Complications: Venous, arterial, and microvascular thrombosis threatens life and limb |
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Warfarin
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requires 5 or more days to achieve full therapeutic effect
- associated with venous limb gangrene when used alone |
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What drugs should be co-administered with Warfarin in HIT and HITT patients?
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systemic anticoagulation should be achieved with an alternative anticoagulant such as argatroban, bivalirudin, lepirudin, and possibly fondaparinux until warfarin is therapeutic
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What is the clinical pentad of TTP?
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FATAL IN UNTREATED
1. Fever 2. Microangiopathic Hemolytic Anemia 3. Thrombocytopenia 4. Renal dysfunction 5. Neurologic deficits (varies: coma, seizures, dysphagia) |
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What does a blood film of a TTP patient show?
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schistocytes and few platelets
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Pathophysiology of TTP
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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, thus leading to end-organ damage, and the appearance of the pentad of clinical features.
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Thrombocytopenia Due to Dilution
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Thrombocytopenia occurs in patients receiving massive transfusions (10-20 units) of Packed RBCs over a brief time frame due to the absence of viable platelets in stored PRBCs
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Thrombocytopenia due to Platelet Distribution
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in moderate to massive splenomegaly when an abnormally high percentage of platelets are within the spleen
(result of sclerosis 2ndy to EtOH, amyloidosis, infiltratice dz, gauche's dz) |
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Pseudothrombocytopenia
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Clumping of platelets from blood collection error (failure to mix in anticoagulant)
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Thrombocytosis
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PLT count > 500K
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Mechanisms of Thrombocytosis
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- Thrombosis in 15-20%
- Bleeding in 3-5% Neither typical in patients with reactive thrombocytosis |
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Complications of Thrombocytosis
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- reactive : Cytokine driven (>80% of cases)
- autonomous/clonal/neoplastic (Essential Thromboyctyosis) *worry about ET b/c platelets function poorly |
