Pathology Notes

Practice questions   Platelet disorders © Jun Wang, MD, PhD 1. A 9-year-old boy presents with sudden onset of gum bleeding. He has a history of coughing with running nose two weeks ago. There is no history of trauma. Physical examination reveals a well-nourished boy with normal development. Multiple pin point like hemorrhage spots are seen on his oral mucosa, upper chest and back, as well as arms. Physical examination is otherwise unremarkable. There is no evidence of hematoma. What is most likely abnormal in his laboratory tests? A. Elevated FDP B. Leukocytosis C. Prolonged PT D. Prolonged PTT E. Reduced platelets 2. A 17-year-old girl with Turner syndrome presents with nose bleeding for 2 days. She has had a cold and fever 1 week ago, but recovered without any treatment. Her past history is unremarkable. Physical examination reveals pin point hemorrhage at her upper limbs. No lymphadenopathy or splenomegaly is seen. Her CBC reveals normal range hemoglobin and wh

Practice questions answers Platelet disorders © Jun Wang, MD, PhD 1. E. Petechiae are usually associated with primary hemostasis defects , either vessel or platelet. Elevated FDP is usually associated with fibrinolysis following thrombosis, such as seen in disseminated intravascular coagulation . Leukocytosis is commonly associated with inflammatory neoplastic processes, either should have more relevant clinical presentations. Abnormalities of PT and PTT are usually seen in secondary hemostasis defects . 2. B. Acute onset of isolated thrombocytopenia in an otherwise healthy individual is most likely acute immune thrombocytopenic purpura . Precursor lymphoid neoplasms (Acute lymphoblastic leukemia) usually presents with increase immature lymphocytes, especially lymphoblasts in circulation. Hemolytic-uremic syndrome or atypical hemolytic-uremic syndrome usually has progressive renal failure, hemolytic anemia and schistocytosis. Iron deficiency anemia is unlikely due to normal

Hemolytic-uremic syndrome   Updated: 07/25/2023 © Jun Wang, MD, PhD General features Most common cause of acute kidney injury in children Associated with Shiga-like toxin More common in summer Need to differentiated from TTP Clinical presentations Usually with history of bloody diarrhea Progressive renal failure Microangiopathic (nonimmune, Coombs-negative) hemolytic anemia Thrombocytopenia Neurological presentation less common Key risk factors Bacterial infection, most commonly due to E coli (O157:H7 most common), S dysenteriae, Salmonella typhi, etc “Atypical” HUS Similar clinical presentation but NOT associated with Shiga-like toxin Commonly in adults May occur in any season Usually NO history of bleeding diarrhea Probably genetic defects in complement factor H , membrane cofactor protein (CD46 ), or factor I Excessive activation of complement pathway Poor prognosis, rapid progress to renal failure Key pathogenesis Endothelial injury caused by

Thrombotic thrombocytopenic purpura Updated: 07/25/2023 © Jun Wang, MD, PhD General features Thrombocytopenia resulted from small vessel thrombosis Need to be differentiated from hemolytic-uremic syndrome Clinical presentations Pentad Microangiopathic hemolytic anemia Thrombocytopenic purpura Neurologic abnormalities: Alteration of mental status, seizures, hemiplegia, paresthesias, visual disturbance, and aphasia Fever Renal disease : Abnormal renal functions May have history of bloody diarrhea, need to differentiate from HUS Key pathogenesis ADAMTS13 (Adam is 13) deficiency associated ultra-large von Willebrand factors Deficiency can be either congenital or due to autoantibodies Endotoxic (Escherichia coli O157:H7 and Shigella dysenteriae serotype I) induced endothelial cell secretion of ultra-large von Willebrand factors Ultra-large von Willebrand factors tends to promote platelet adhesion and aggregate, resulting in thro

HIV associated thrombocytopenia Updated: 07/24/2023 © Jun Wang, MD, PhD General features Most common cause of thrombocytopenia in HIV-infected patients Either direct HIV infection of hematopoietic stem cells or immune process Clinical presentations HIV test may be considered in patient with unexplained thrombocytopenia May have splenomegaly Key pathogenesis Probably ineffective platelet production and increased peripheral platelet destruction Key Laboratory findings Thrombocytopenia Other findings associated with HIV infection Back to thrombocytopenia Back to bleeding disorders Back to contents

Heparin-induced thrombocytopenia Updated: 07/24/2023 © Jun Wang, MD, PhD General features Complication of heparin therapy More commonly associated with unfractionated heparin (UFH) than low molecular weight heparin (LMWH) Type I :   Presents within the first 2 days after exposure to heparin , and the platelet count normalizes with continued heparin therapy, nonimmune disorder resulted from direct effect of heparin on platelet activation Type II :   Immune-mediated disorder, typically occurs 4-10 days after exposure to heparin , life- and limb-threatening thrombotic complications, THE HIT when discussed   Diagnosis based on History of heparin usage Clinical presentations of thromboembolism Thrombocytopenia   Laboratory studies of HIT antibodies Clinical presentations Thromboembolism Most commonly venous thrombosis 4Ts T hrombocytopenia T iming of platelet count drop, typically 5-14 days, or less in one day if previously exposed to heparin T hrombosi

Chronic immune thrombocytopenia   Updated: 07/24/2023 © Jun Wang, MD, PhD General features Typically in adults aged 20-40 years More common in women Usually do not have history of viral infection Associated with alterations in immune homeostasis Diagnosis of exclusion in patients with isolated thrombocytopenia Clinical presentations Insidious onset, usually NO precipitating causes Most commonly bleeding in skin or mucosa Severe hemorrhage uncommon May have splenomegaly Key pathogenesis Clonal expansion of CD8+ cytotoxic T cells may act independently of autoantibodies Autoantibodies against platelet GPIIb/IIIa or GPIb/IX Reduced platelet lifespan due to antibody-mediated destruction   Impaired platelet production due to megakaryocytes damage Key Laboratory findings Isolated thrombocytopenia Positive anti-platelet antibodies Negative anti-platelet tests could NOT rule out ITP Key morphological features Normal to increased megakaryocytes Need to ex

Acute immune thrombocytopenia   Updated: 07/24/2023 © Jun Wang, MD, PhD General features Self-limited, usually weeks Almost exclusively in children Usually preceded by a viral infection (varicella, mononucleosis) or vaccination Usually clinical diagnosis based on Well appearing patient Mucocutaneous bleeding No systemic signs Isolated thrombocytopenia Clinical presentations Sudden onset Presentations depending on platelet count Mild bleeding/petechiae, unless platelet < 20 x 10 3 /mm 3 NOT ITP if with lymphadenopathy or splenomegaly, usually suggestive of secondary thrombocytopenia Key pathogenesis May be associated with auto-reactive cytotoxic T cells, or autoantibodies against platelet membrane components Probably due to exposure of cryptantigens or pseudoantigens Key Laboratory findings Isolated thrombocytopenia Key morphological features Megakaryocyte hyperplasia Back to thrombocytopenia Back to bleeding disorders Back to conten

Reactive thrombocytosis Updated: 08/12/2020 © Jun Wang, MD, PhD Etiology Infection Postsurgical status Malignancy Postsplenectomy state Acute blood loss or iron deficiency Clinical features No need to correct platelet count Back to bleeding disorders Back to contents

Bleeding disorders due to abnormal platelet function Updated: 08/12/2020 © Jun Wang, MD, PhD General features Inherited or acquired Three large categories Defects of adhesion Defects of aggregation Disorders of platelet secretion Glanzmann’s disease Qualitative or quantitative deficiencies of the fibrinogen receptor GPIIb/IIIa Platelet type bleeding of mucosa, skin, etc Management: Avoidance of medications that affect platelet function, treatments of anemia, etc Platelet transfusion for bleeding patients Recombinant Factor VIIa may be considered Bernard-Soulier Syndrome Group of hereditary platelet disorders characterized by Thrombocytopenia Giant platelets Qualitative platelet defects Absence or decreased expression of the GPIb/IX/V complex , a receptor for von Willebrand factor, on the surface of the platelets Autosomal recessive Clinical presentations: Easy bruising, bleeding Treatment: Supportive, may consider DDAVP, or similar approach

Thrombocytopenia   Updated: 08/03/2021 © Jun Wang, MD, PhD General features Platelet count below the lower limit of normal, either reduced production or increased destruction Grades Mild (platelet count 100-150 x 10 3 /mm 3 ) Moderate (50-99 x 10 3 /mm 3 ) Severe (<50 x 10 3 /mm 3 ) Usually asymptomatic until platelet count <100 x 10 3 /mm 3 Surgical bleeding <50 x 10 3 /mm 3 Spontaneous bleeding <10 x 10 3 /mm 3 Clinical presentations Asymptomatic, ISOLATED, incidentally-discovered thrombocytopenia Common: Immune thrombocytopenia (ITP) , Gestational thrombocytopenia during pregnancy Less common: Occult liver disease, myelodysplastic syndrome , congenital thrombocytopenia, HIV infection Symptomatic, severe thrombocytopenia Drug-induced thrombocytopenia Immune thrombocytopenia (ITP) Thrombocytopenia as part of a multisystem illness Common : Immune thrombocytopenic purpura, drug-induced thrombocytopenia, heparin-induced thrombocytopenia

Bleeding disorders   Updated: 09/16/2020 © Jun Wang, MD, PhD Hemostasis Primary: Vasoconstriction, platelet activation Secondary: Coagulation cascades Results: Blood clot formation Activation of platelets Coagulation system Intrinsic pathway: XII, XI, IX, VIII (8-12 except 10) Extrinsic pathway: VII Common pathway: X, V, prothrombin (II), fibrinogen (I) (4 smallest US dollar bills) Etiology of bleeding disorders Vascular dysfunction, including vitamin C deficiency, telangiectasia, allergic purpura, purpura associated with infections such as meningococcus and Rocky Mountain spotted fever, etc Platelet disorders Thrombocytopenia Thrombocytosis Platelet dysfunctions associated with uremia, MDS , medications (NSAIDs etc) Bernard-Soulier syndrome, etc Coagulopathy Von Willebrand disease Hemophilia A Hemophilia B Acquired hemophilia Liver disease associated coagulopathy Vitamin K deficiency, including warfarin associated coagulopathy Other