Question

1. Complete the following table to demonstrate comparison of pathophysiology, platelet findings, and clinical symptoms associated with platelet disorders

Platelet Disorder	Pathophysiology	Platelet Findings Other Findings if applicable	Patient Symptoms
Drug‐induced thrombocytopenia [quinines, NSAIDs, heparin, sulfonamides, amoxicillin, diuretics]
Idiopathic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Hemolytic uremic syndrome
Essential thrombocytosis
Von Willebrand disease
Bernard‐Soulier syndrome
Glanzmann’s thrombasthenia
Aspirin

Answer 1

Disorder	pathophysiology	platelet findings	patient symptoms
Drug-induced thrombocytopenia (quinines, NSAIDS, heparin, sulfonamides, amoxicillin. diuretics)	Quinines, sulfonamides, NSAIDs: Mechanism: drug dependent antibody Description: Drug interacts noncovalently with platelet membrane glycoprotein, antibody binds to drug-glycoprotein complex Penicillin derivatives: Mechanism: Hapten dependent Description: drug forms covalent linkage with membrane glycoprotein, to act as a hapten to induce Drug dependent antibody(DDA) response Heparin: Mechanism: Immune complex Description: drug reacts with platelet factor 4 and produces an antigenic complex. Antibodies react against the antigenic complex to form immune complexes, that binds to platelet fc receptor, resulting in platelet activation.	Moderate : <50000 / L Severe: <10000/L	petechiae (red spots on the skin), abnormal vaginal/ rectal/ oral/ nasal bleeding, gastrointestinal bleeding, excessive bruising over minor fall, headache(in severe cases)
Idiopathic thrombocytopenic purpura	due to autoantibody- mediated destruction of macrophages in spleen, and moderaately impaired platelet production due to antibody and/ or cytotoxic T-cell mediated megakaryocytic damage, the platelet mass shrinks as a result of accelerate platelet clearance.	Moderate: <100000 severe: <10000	Purpura(purple spots under the skin), petechiae, excessive bleeding during surgery, abnormal oral/nasal/rectal/vaginal bleeding, blood in urine or stool
Thrombotic thrombocytopenic purpura	involves nonimmunologic platelet destrcution. loose strands of platelets and fibrin are deposited in multiple vessels and damage passing platelets and RBCs, causing thrombocytopenia. consumption of platelet within multiple small thrombi also contribute to thrombcytopenia. Antibodies inhibit the enzyme ADAMTS13 (von willebrand cleaving protease, a protein involved in blood clotting) which results in decrease of breakdown of large multimers of von willebrand factor	<30 x109 /L	Purpura, petechiae, jaundice, fatigue, fever, low urine output, headache, seizure, stroke, confusion, speech changes, shortness of breath
Hemolytic uremic syndrome	Shiga toxins (STx1, STx2) are released by E.coli in the intestine > absorption of the toxin by the epithelium of the gastrointestinall system> reaches target organ > binds to globotriosylceramide (Gb3, a glycopeptide surface receptor in the epithelium of the target organ)> inhibits protein synthesis>endothelial damage> cell death, inflammatory response, thrombocyte activation	<150000/mm3	bloody diarrhea, abdominal pain, cramping, vomiting, pale skin, fever, fatigue, abdominal swelling, confusion, decreased urine output
Essential thrombocytosis	a point mutation chnging aminoacid valine to phenylalanine at codon 617 of the JAK2 gene causing myeloproliferative neoplasms presence of megakaryocytic hyperplasia in the bone marrow	>450000 / microL	headache, dizziness, chest pain, numbness, throbbing/ burning pain, redness hands and feet, vision changes, abnormal vaginal/ rectal/ oral/ nasal bleeding, bloody stool
Von Willebrand disease	defect in the van willebrand factor.	normal	abnormal vaginal/ rectal/ oral/ nasal bleeding excessive bleeding during childbirth, excessive bruising over minor fall
Bernard-Soulier syndrome	mutation in: GPI b GPI b GPIX	thrombocytopenia	nosebleeds, heavy menstrual flow, excessive bleeding
Glanzmann's thrombasthenia
Aspirin