Bleeding Disorders PDF

Bleeding Disorders & Michael Yakubovskyy, MD, PhD 1 LOs LO# LO 1 2 3 4 5 6 Explain the process of hemostasis, and the role of the hemostatic and anti-hemostatic factors; interpret screening tests in evaluation of hemostasis; define hemorrhagic diathesis Describe and recognize the features...

Bleeding Disorders & Michael Yakubovskyy, MD, PhD 1 LOs LO# LO 1 2 3 4 5 6 Explain the process of hemostasis, and the role of the hemostatic and anti-hemostatic factors; interpret screening tests in evaluation of hemostasis; define hemorrhagic diathesis Describe and recognize the features of hemorrhagic diathesis associated with the following vascular wall abnormalities - Meningococcemia - Bacterial endocarditis - Microscopic polyangiitis - Henoch-Schönlein purpura - Scurvy - Ehlers-Danlos syndrome - Hereditary hemorrhagic teleangiectasia (Weber-Osler-Rendu syndrome) Compare and contrasts the following quantitative platelet abnormalities - Thrombotic thrombocytopenia purpura (TTP) - Hemolytic uremic syndrome (HUS) - Immune thrombocytopenia purpura (ITP) - Heparin-induced thrombocytopenia (HIT) in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis Describe the following qualitative platelet abnormalities - Bernard-Soulier syndrome - Glanzmann thrombasthenia - Platelet abnormalities in uremia and aspirin administration Compare and contrasts the following abnormalities in clotting factors - Hemophilia A - Hemophilia B - Vitamin K deficiency in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis Describe the etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis of the following mixed platelet and clotting factor abnormalities - von Willebrand disease 2 - Disseminated intravascular coagulation (DIC) LO1. Explain the process of hemostasis, and the role of the hemostatic and anti-hemostatic factors; interpret screening tests in evaluation of hemostasis; define hemorrhagic diathesis Hemorrhagic Diathesis • Regular and multiple bleeding = hemorrhagic/bleeding diathesis • Major manifestations – Mucosal bleeding: epistaxis, hemoptysis, hematuria, menorrhagia, hematochezia, melena, etc. – Skin bleeding • Petechiae: 1-2 mm in d • Purpura: 3-10 mm in d • Ecchymoses (bruises): >1 cm in d • Hematoma: collection of blood inside ecchymosis or large purpuric lesions (“palpable purpura”) – Intraarticular bleeding (hemarthroses) – Intracranial bleeding in severe cases (subarachnoid and intracerebral 6 hemorrhages) LO1. Explain the process of hemostasis, and the role of the hemostatic and anti-hemostatic factors; interpret screening tests in evaluation of hemostasis; define hemorrhagic diathesis Petechiae in Meningococcemia (Left) and Rocky Mountain Spotted Fever (Right), Gross 7 LO1. Explain the process of hemostasis, and the role of the hemostatic and anti-hemostatic factors; interpret screening tests in evaluation of hemostasis; define hemorrhagic diathesis Purpura in Henoch-Schönlein Purpura (Left), and Confluent Palpable Purpura in Microscopic Polyangiitis (Right), Gross 8 LO1. Explain the process of hemostasis, and the role of the hemostatic and anti-hemostatic factors; interpret screening tests in evaluation of hemostasis; define hemorrhagic diathesis Ecchymoses in Hemophilia A (Left) and Warfarin Overdose (Right), Gross 9 LO1. Explain the process of hemostasis, and the role of the hemostatic and anti-hemostatic factors; interpret screening tests in evaluation of hemostasis; define hemorrhagic diathesis Classification of Bleeding Disorders • Bleeding disorders due to vessel wall abnormalities • Bleeding disorders due to platelet abnormalities (abnormalities in primary plug formation) – Quantitative disorders (thrombocytopenia) – Qualitative disorders (disorders of platelet function) • Bleeding disorders due to clotting factors abnormalities (abnormalities in secondary plug formation) • Mixed bleeding disorders due to both platelet and clotting factor abnormalities 10 LO2. Describe and recognize the features of hemorrhagic diathesis associated with the following vascular wall abnormalities … Bleeding Disorders due to Vessel Wall Abnormalities, Classification • Infections: meningococcemia, bacterial (infective) endocarditis, rickettsioses • Small vessel vasculitides: microscopic polyangiitis, Henoch-Schönlein purpura, etc. • Collagen defects: scurvy and Ehlers-Danlos syndrome • Hereditary hemorrhagic teleangiectasia (Weber-OslerRendu syndrome) • Vascular amyloidosis 11 LO2. Describe and recognize the features of hemorrhagic diathesis associated with the following vascular wall abnormalities … Bleeding Disorders due to Vessel Wall Abnormalities, Manifestations and Tests • Clinical manifestations: hemorrhagic diathesis – With petechiae and purpura as the most common type of bleeding • Laboratory tests – Normal PC – Normal BT – Normal PT – Normal PTT 12 LO2. Describe and recognize the features of hemorrhagic diathesis associated with the following vascular wall abnormalities … Petechiae Associated with Hair Follicles in Scurvy (Left) and Purpura in Meningococcemia (Right), Gross 13 LO2. Describe and recognize the features of hemorrhagic diathesis associated with the following vascular wall abnormalities … Hereditary Hemorrhagic Teleangiectasia (Weber-Osler-Rendu Disease), Gross 14 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis Platelet Abnormalities: Classification • Quantitative disorders – Thrombocytopenias with microangiopathic hemolytic anemia (MAHA) • Thrombotic thrombocytopenia purpura (TTP) • Hemolytic uremic syndrome (HUS) – Immune thrombocytopenia purpura (ITP) – Drug-induced thrombocytopenia • Heparin-induced thrombocytopenia – HIV-associated thrombocytopenia • Qualitative disorders – – – – Bernard-Soulier syndrome Glanzmann thrombasthenia Uremia Aspirin administration 15 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis Platelet Disorders: Clinical and Laboratory Manifestations • Clinical features: hemorrhagic diathesis with all possible manifestations • Laboratory findings – Thrombocytopenia in quantitative disorders: ↓ platelet count (PC) < 100,000/µL (except qualitative disorders; RR: 150,000-350,000/µL) • <50,000/µL —> severe posttraumatic bleeding • <20,000/µL —> spontaneous (non-traumatic) bleeding – Bleeding time (BT, RR: 2 - 9 min): ↑ – PT and PPT: normal (no activation of coagulation cascade)16 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis Thrombotic Thrombocytopenic Purpura (TTP) • Classification and demographics •Acquired TTP: common, affects adult women, develops as an abnormal immune response common •Genetic TTP: rare, appears in adolescents, symptoms are episodic • NB: from this point, only acquired TTP is covered and the term TTP is used to designate the disorder 17 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis TTP, Pathogenesis 1. Production of antibodies against vWF-cleaving protease (ADAMTS13) 2. Inability to cleave active vWF multimers into inactive vWF monomers 3. Accumulation of (active) vWF multimers in the blood 4. Spontaneous platelet activation and aggregation 5. Formation of platelet microthrombi 6. Consumption thrombocytopenia 18 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis TTP, Manifestations and Prognosis • Clinicopathologic manifestations (pentad) 1. Hemorrhagic diathesis: petechiae, purpura, and ecchymoses 2. MAHA 3. Fever 4. Acute kidney injury (microthrombi in glomerular vessels) —> oliguria, proteinuria, ↓GFR, ↑Cr, and ↑BUN 5. CNS abnormalities (microthrombi in microvessels) [more common in TTP than in HUS] —> headache, focal neurologic deficit, confusion, and coma • Prognosis: TTP is a life-threatening condition and requires immediate intervention 19 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis TTP: Labs • • • • • • • • ↓ PC (thrombocytopenia) ↑ BT Normal PT Normal PTT MAHA (schistocytes) ↑ megakaryocyte count in bone marrow ↓↓ ADAMTS13 activity (+) Antibodies against ADAMTS13 20 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis TTP: Confluent Petechiae on the Oral Mucosa, PetechialPurpuric Skin Rash, and Ecchymoses, Gross 21 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis TTP, Schistocytes in the PBS and Thrombi in the Hilar Glomerular Vessels, Micro :Thrombi_in_patient_with_thrombotic_thrombocytopenic_purpura_.jpg Erhabor Osaro (Associate Professor), CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons 22 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis Hemolytic-Uremic Syndrome (HUS) • Demographics: children • Etiology: E.coli (O157:H7) infection • Pathogenesis 1. Bloody diarrhea (dysentery) 2. Release of Shiga-like toxin 3. Endothelial damage 4. Formation of platelet microthrombi 5. Consumption thrombocytopenia 23 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis HUS, Manifestations and Prognosis • Clinicopathologic manifestations (pentad) 1. Hemorrhagic diathesis, probably less severe than in TTP 2. MAHA 3. Fever 4. Acute kidney injury ( (microthrombi in glomerular vessels) —> oliguria, proteinuria, ↓GFR, ↑Cr, and ↑BUN [more common and severe in HUS than in TTP] 5. CNS abnormalities (microthrombi in microvessels) • Prognosis: a self-limited condition, supportive treatment is beneficial 24 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis • • • • • • HUS: Labs ↓ PC (thrombocytopenia) ↑ BT Normal PT Normal PTT Hemolytic anemia with schistocytes ↑ megakaryocytic count in bone marrow 25 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis HUS, Schistocytes in the PBS, Thrombosis (Arrow) and Collapse of the Glomerular Vessels (Silver Stain), Micro 26 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis Immune Thrombocytopenic Purpura (ITP) • Classification and demographics •Chronic ITP: common, severe, affected population: adult females < 40 yrs •Acute ITP: rare, self-limited, affected population: children • Etiology: abnormal immune response •Chronic ITP: autoimmune diseases (SLE), viral infections, malignancies, drug reactions •Acute ITP: preceding acute viral illness • NB: from this point, only chronic IPT is covered, and the term ITP is used to designate the disorder 27 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis ITP, Pathogenesis 1.Production of anti-platelet antibodies (IgG) against GPIIb/IIIa and/or GPIb-IX 2.Antibody-platelet complex formation 3.Recognition of IgG Fc receptors by macrophages 4.Clearance of immune complexes by splenic macrophages 5.Thrombocytopenia 28 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis ITP: Manifestations and Prognosis • Manifestations: hemorrhagic diathesis; in severe cases – Confluent petechiae, purpura, and ecchymoses – Intracranial hemorrhages • Prognosis: good with treatment – Splenectomy is recommended in refractory cases 29 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis ITP: Tests • Bleeding tests – ↓ PC – ↑ BT – Normal PT – Normal PTT • Bone marrow: ↑ number of megakaryocytes and their immaturity • PBS: abnormally large platelets (megathrombocytes) 30 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis ITP, Petechiae and Purpura (Left), Petechiae and Ecchymoses (Center), Buccal Ecchymoses (Right), Gross 31 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis ITP, Increase Number of Megakaryocytes in BM (Right), Control (Left), Micro https://commons.wikimedia.org/wiki/File:Trilineage_hematopoiesis_(original).jpg Mikael Häggström, M.D. Author info - Reusing images- Conflicts of interest: None Mikael Häggström, M.D.Consent note: Consent from the patient or patient's relatives is regarded as redundant, because of absence of identifiable features (List of HIPAA identifiers) in the media and case information (See also HIPAA case reports guidance)., CC0, via Wikimedia Commons 32 LO3. Compare and contrasts the following quantitative platelet abnormalities … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis Heparin-Induced Thrombocytopenia (HIT) • Type I HIT: high or low molecular weight heparin (HMWH or LMWH) administration —> platelet aggregation —> mild-moderate thrombocytopenia • Type II HIT, mechanism 1. 1-2 weeks after HMWH administration 2. Immune response with antibody production 3. Formation of HMWH+PF4+antibody complexes 4. Platelet activation and aggregation 5. Thrombosis: large arteries and veins, deep vein thrombosis (DVT), pulmonary thromboembolism [medical emergency] 6. Thrombocytopenia 33 LO5.Compare and contrasts the following abnormalities in clotting factors … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis Clotting Factors Abnormalities: Common linical Features and Laboratory Tests • Clinical features: hemorrhagic diathesis with large posttraumatic hematomas (e.g., hemarthrosis) and prolong bleeding after a laceration or surgical procedure (e.g., after tooth extraction) • Laboratory findings – Normal platelet count – Normal bleeding time – ↑ PT and/or ↑ PPT depending on the cascade involved • ↑ INR in patients on warfarin treatment – ↓ plasma level of the factor(s) affected 35 LO5.Compare and contrasts the following abnormalities in clotting factors … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis Elbow Hemarthrosis with Ecchymosis in a Patent with Hemophilia A 36 LO5.Compare and contrasts the following abnormalities in clotting factors … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis Clotting Factor Abnormalities: Classification • Hemophilia A (FVIII deficiency) • Hemophilia B (Christmas disease of FIX deficiency) • Vit K deficiency 37 LO5.Compare and contrasts the following abnormalities in clotting factors … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis Hemophilia A • Common • X-linked recessive – De novo mutations possible • Hemorrhagic diathesis with severe post-traumatic and prolong aftersurgery bleeding • Labs – Normal PC – Normal BT – Normal PT – ↑ PTT – ↓ FVIII 38 LO5.Compare and contrasts the following abnormalities in clotting factors … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis Hemophilia B • Less common than hemophilia A • X-linked recessive – De novo mutations possible • Hemorrhagic diathesis with severe post-traumatic and prolong aftersurgery bleeding • Labs – Normal PC – Normal BT – Normal PT – ↑ PTT – ↓ FIX Stephen Christmas, the 1st patient diagnosed with hemophilia B 39 LO5.Compare and contrasts the following abnormalities in clotting factors … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis Vitamin K Deficiency • Etiology of vitamin K deficiency – Long-term antibiotic therapy: inhibition of vitamin K-producing bacteria in the GI tract – Malabsorption: deficiency of fat-soluble vitamins, including vitamin K – In newborns: lack of GI colonization by bacteria that normally synthesize vitamin K • Physiologic role of vitamin K: contributes to synthesis of FII, VII, IX, X, and proteins C and S in the liver • Coagulation effects of vitamin K deficiency – – – – Deficiency Deficiency Deficiency Deficiency in intrinsic pathway (FIX) in extrinsic pathway (FVII) in common pathway (FX and FII) in anticoagulant proteins C and S 40 LO5.Compare and contrasts the following abnormalities in clotting factors … in terms of etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis Vitamin K Deficiency: Manifestations and Lab Tests • Net result of vitamin K deficiency: hemorrhagic diathesis (depression of coagulation cascade is more severe than depression of anticoagulant factors) • Labs – Normal PC – Normal BT – ↑ PT – ↑ PTT – ↓ FIX, VII, X, and II – ↓ Protein C and S 41 LO6. Describe the etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis of the following mixed platelet and clotting factor abnormalities: von Willebrand disease and disseminated intravascular coagulation (DIC) Mixed Platelet and Clotting Factor Abnormalities, Classification • von Willebrand disease: a group of genetic disorder with vWF mutations – The most common inherited bleeding disorder – Three types, all autosomal dominant • Disseminated intravascular coagulation (DIC): a thrombo-hemorrhagic disorder that starts with excessive coagulation in microvasculature and finishes with consumption of platelets and clotting factors and following bleeding 42 LO6. Describe the etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis of the following mixed platelet and clotting factor abnormalities: von Willebrand disease and disseminated intravascular coagulation (DIC) von Willebrand Disease • Etiology: a point mutation in vWF gene • Pathogenesis (associated more with deficiency in coagulation cascade than in platelet adhesion) 1. Defective vWF 2. Inability to stabilize FVIII 3. Deficient FVIII support to FIXa in FX activation 4. Hemorrhagic diathesis, usually mild-moderate • Hemarthroses are seen rarely 43 LO6. Describe the etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis of the following mixed platelet and clotting factor abnormalities: von Willebrand disease and disseminated intravascular coagulation (DIC) von Willebrand Disease: Laboratory Tests • • • • • • Normal PC (platelets are not affected) ↑ BT (defective vWF —> reduced platelet adhesion) Normal PT (extrinsic pathway is not involved) ↓ FVIII (inadequate stabilization by defective vWF) ↑ PTT (low FVIII —> reduced ability of FIXa to activate FX) Abnormal ristocetin test – Ristocetin test: in laboratory setting, ristocetin molecules facilitate binding between vWF and GPIb-IX with following activation of platelet clumping. Mutated vWF cannot bind GPIb-IX, therefore platelets do not clump 44 LO6. Describe the etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis of the following mixed platelet and clotting factor abnormalities: von Willebrand disease and disseminated intravascular coagulation (DIC) Disseminated Intravascular Coagulation (DIC) • DIC: a combination of two distinct processes – Widespread coagulation in microcirculation – Platelet and clotting factors consumption that leads to hemorrhagic diathesis with massive bleeding from mucosal membranes and IV sites • DIC is not a primary disease, but rather of a complication of – Massive trauma (or extensive surgery, or severe burns) with tissue factor release – Sepsis (endotoxins inhibit thrombomodulin and activate FXII) – Obstetric pathologic conditions (preeclapsia, retained dead fetus,, dead fetus, amniotic fluid embolism, acute fatty liver of pregnancy) – Acute promyelocytic leukemia and adenocarcinomas (malignant tumors from glandular tissues release mucin that activates coagulation)45 LO6. Describe the etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis of the following mixed platelet and clotting factor abnormalities: von Willebrand disease and disseminated intravascular coagulation (DIC) DIC: Clinicopathologic Features • Onset: acute or chronic • Leading manifestations: disorders of hemostasis – Hemorrhagic diathesis • Petechiae, purpura, and ecchymoses • Bleeding (generalized oozing) from wound sites, IV lines, mucosal surfaces, intracranial hemorrhage – and/or Thrombosis (common in cancer patients): DVT, arterial thrombosis and ischemia, etc. • Mostly affected organs: kidney, adrenals, brain, lungs, and liver • Common morphologic changes: fibrin microthrombi, microinfarcts, and tiny hemorrhages 46 LO6. Describe the etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis of the following mixed platelet and clotting factor abnormalities: von Willebrand disease and disseminated intravascular coagulation (DIC) • • • • • • • DIC: Labs ↓ PC (thrombocytopenia) ↑ BT ↑ PT ↑ PTT ↓ Fibrinogen ↑ D-dimers (or FDPs) MAHA (schistocytes) 48 LO6. Describe the etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis of the following mixed platelet and clotting factor abnormalities: von Willebrand disease and disseminated intravascular coagulation (DIC) DIC: Organ-Specific Clinicopathologic Features • Kidneys: fibrin thrombi in the glomeruli, and bilateral renal cortical necrosis —> acute kidney injury • Adrenals: bilateral adrenal hemorrhages in meningococcemia (Waterhouse-Friderichsen syndrome) —> acute adrenal insufficiency • Brain: nonspecific morphologic changes —> focal neurologic deficit, confusion, and coma • Blood: microangiopathic hemolytic anemia 49 LO6. Describe the etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis of the following mixed platelet and clotting factor abnormalities: von Willebrand disease and Disseminated intravascular coagulation (DIC) DIC, Fibrin Thrombi in Glomerular Vessels (PAS - Left and PTAH* - Right), Micro By Paulo Henrique Orlandi Mourao - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8823735 https://commons.wikimedia.org/wiki/File:Kidney_DIC_with_Glomerular_Thrombi_(PTAH)_(1858196353).jpg Ed Uthman from Houston, TX, USA, CC BY 2.0 <https://creativecommons.org/licenses/by/2.0>, via Wikimedia Commons *PTAH (PHosphotungstic Acid - Hematoxylin): fibrin -blue, collagen - reddish 50 LO6. Describe the etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis of the following mixed platelet and clotting factor abnormalities: von Willebrand disease and disseminated intravascular coagulation (DIC) Renal Cortical Infarct (Right), Control (Left), Gross • Cortex: pale diffusely including pyramids (necrotic) • Medulla: dark red (hyperemic) Courtesy to WebPath https://commons.wikimedia.org/wiki/File:Kidney_%E2%80%93_acute_cortical_necrosis.jpg 51 Haymanj, Public domain, via Wikimedia Commons LO6. Describe the etiology, pathogenesis, morphologic changes, clinical manifestations, laboratory evaluations, and prognosis of the following mixed platelet and clotting factor abnormalities: von Willebrand disease and disseminated intravascular coagulation (DIC) TTP, HUS, and DIC Differential Diagnosis, Table Parameters Fever GI symptoms (nausea, vomiting, abdominal pain) Renal manifestations (oliguria, proteinuria, ↓GFR, ↑Cr, ↑BUN) CNS symptoms (headache, focal deficit, confusion, coma) MAHA (schistocytes) Platelet count Bleeding time PT PT Fibrinogen D-dimers (FDPs) ADAMTS13 activity Antibodies agains ADAMTS13 TTP HUS DIC + ++ + ++ +++ ↓↓ ↑ Normal Normal Normal Normal ↓↓ +++ + ++ +++ + +++ ↓ ↑ Normal Normal Normal Normal Normal - + + + + +++ ↓↓ ↑ ↑ ↑ ↓ ↑ Normal -52 The End 53