Platelet Disorders MCQs

Thrombocytopenia and anti-platelets antibodies in a child presenting with purpura after 2 weeks of viral illness is characteristic of ITP Reference : Robbins 9th/pg 659; 8th/pg 669

Acute immune thrombocytopenic purpura (ITP) and chronic ITP are caused by antiplatelet autoantibodies, but the acute form is typically seen in children after a viral disease. If the bone marrow was aplastic, all cell lines should be reduced. Glycoprotein IIb/IIIa dysfunction/ deficiency can be seen with Glanzmann thrombasthenia and chronic ITP. Scurvy caused by vitamin C deficiency leads to increased capillary fragility with ecchymoses, but not to thrombocytopenia. Reference: Robbins & cotran pathologic basis of diseases 10 th edition, Chapter 4, pg 118

Bernard-Soulier syndrome illustrates the consequences of defective adhesion of platelets to subendothelial matrix. Bernard-Soulier syndrome is caused by an inherited deficiency of the platelet membrane glyco protein complex Ib-IX. This glycoprotein is a receptor for vWF and is essential for normal platelet adhesion to the subendothelial extracellular matrix Reference : Robbins 9th/pg 660

Thrombopoietin (TPO) is the principal physiologic regulator of platelet production. In vitro, TPO induces the growth of colony-forming units-megakaryocyte (CFU-MK) and the generation of mature polyploid megakaryocytes, which subsequently form extended cytoplasmic processes, termed proplatelets. The liver secrets thrombopoietin at a constant rate into the circulation, where it bind to c-mpl ligands on both platelets and megakaryocytes. Thrombopoietin bound to platelets are internalized and degraded and thrombopoietin bound to platelets stimulates platelet production. Reference: Mitchell, Oscar et al. 'The pathophysiology of thrombocytopenia in chronic liver disease. 'Hepatic medicine: evidence and research vol. 8 39-50. 15 Apr. 2016, doi:10.2147/HMER.S74612

VWF has a central role in primary haemostasis where it mediates platelet adhesion to damaged vascular subendothelium and subsequently platelet aggregation. Following a vascular injury, VWF binds specifically to fibrillar collagen type I and III. The below figure explains Structure and function of factor VIII-von Willebrand factor (vWF) complex. Factor VIII and vWF circulate as a complex. vWF also is present in the subendothelial matrix of normal blood vessels. Factor VIII takes part in the coagulation cascade by activating factor X by means of factor IX (not shown). vWF causes adhesion of platelets to subendothelial collagen, primarily through the glycoprotein Ib (GpIb) platelet receptor. Reference : Robbins, 10th edition, page number - 489

Glanzmann's thrombasthenia is an abnormality of the platelets. It is an extremely rare coagulopathy (bleeding disorder due to a blood abnormality), in which the platelets contain defective or low levels of glycoprotein IIb/IIIa (GpIIb/IIIa), which is a receptor for fibrinogen. As a result, no fibrinogen bridging of platelets to other platelets can occur, and the bleeding time is significantly prolonged. Characteristically, there is increased mucosal bleeding Heavy menstrual bleeding Easy bruising Nosebleeds Bleeding from the gums Gastrointestinal bleeding Postpartum bleeding Increased postoperative bleeding. Reference: https://en.wikipedia.org/w/index.php?title=Glanzmann%27s_thrombasthenia&oldid=1075482842

Platelets are disc-shaped anucleate cell fragments that are shed from megakaryocytes in the bone marrow into the bloodstream. Their function depends on several glycoprotein receptors, a contractile cytoskeleton, and two types of cytoplasmic granules. α-Granules have the adhesion molecule P-selectin on their membranes and contain proteins involved in coagulation, such as fibrinogen, coagulation factor V, and vWF, as well as protein factors that may be involved in wound healing, such as fibronectin, platelet factor 4 (a heparin-binding chemokine), platelet-derived growth factor (PDGF), and transforming growth factor-β. Dense (or δ) granules contain adenosine diphosphate (ADP) and adenosine triphosphate, ionized calcium, serotonin, and epinephrine. Reference : Robbins, 10th edition, page number - 102

Platelets attach to exposed surface of endothelium following injury; this adhesion is mediated by vWF, which binds to GpIb receptors on platelets. This intiates activation of platelets, which change shape of platelets from a disc to sphere and release their contents to the exterior. These are mainly adenosine diphosphate (ADP), serotonin and thromboxane A2. Platelet aggregation (sticking of platelets to each other) is mediated by thromboxane A2, collagen, ADP and thrombin. Binding of ADP to platelets causes exposure of GpIIb/IIIa receptors which bind fibrinogen. Fibrinogen binding to multiple platelets causes formation of large platelets aggregates. Reference :Essentials of clinical pathology, 2nd edition, page number - 320