Heme/Onc - Week 3 Review - Part 2 Flashcards
(49 cards)
Primary Hemostasis - 3 Major Steps
1) Trasient Vasoconstrition (Neurogenic + Endothelial Release)
2) Platelet Adhesion (vWF binds sub-endothelial collagen + GP1b from Platelets)
3) Platelet Aggregation - Platelets bind vWF + Each other via GPIIB/IIIA - Release granules with TXA2 + ADP)
vWF Production - 2 Places
1) Alpha Granules of Platelets
2) Wiebl-Palade Bodes if Endothelial Cells (Also produce p-selectin for speed bumps in inflammation)
Disorders of Primary Hemostasis - 2 Major Classes + 6 Disorders
Disorders of Platelet Quantity
1) Acute Immune Thrombocytopenic Purpura
2) Chronic Immune Thrombocytopenic Purpura
3) Microangiopathic Hemolytic Anemia - Thrombocutopenic Purpura
4) Hemolytic Uremia Syndrome - Microangiopathic Hemolytic Anemia
Disorders of Platelet Quality
5) Bernard Soulier
6) Glanzmann Disroder
Major Features of Primary Hemostatsis (5)
1) Skin + Mucousal Bleeding
2) Petechia = Thrombocytopenia
3) Low Platelet Count
4) High Bleeding Time
5) Normal PT/PTT (No Coagulation Factors involved)
Immune Thrombocytoic Purpura (ITP) - 2 Forms + Pathopyhsiology
Acute - Children after Viral Infection
Chronic - Adults - SLE + CLL
Autoimmune IgG Antibody against Platelets Antigen (GPIIb/IIIa) - Antibody bound platelets consumed in macrophages
Immune Thrombocytoic Purpura (ITP) - Key Lab Findings (4) + Treatment (2)
Findings
1) Large Platelets
2) Increase MK Cells in Marrow
3) Thrombocytopenia
4) Long Bleeding Time with Normal PT/PTT
Treatment
1) Steroids
2) IVIgG
Fetal-Maternal ITP - Key Facts (2)
1) Material IgG attacks fetal platelets
2) HPA-1A = Most Common
Microangiopathic Hemolytic Anemia - Definition Causes (4) + Classic Findings (3)
Anemia caused by RBC desctruction when the crash into micro-thrombi - causes using up/damage to platelets
Causes
1) TTP
2) HUS
3) DIC
4) Mechanical Heart Valves
Classic FIndings
1) Skin/Mucosal Bleeding (vs. Joints in Secondary Hemostasis disoders)
2) Renal Symptoms (worse in HUS)
3) CNS Symptoms (worse in TTP)
Microangiopathic Hemolytic Anemia - Lab Findings (5)
1) Thromboyctopenia
2) Normal PT/PTT with elevated Bleeding Time
3) Schistocytes (Half cells with points from microthrombi damage)
4) Increased Mega-K Cells in Marrow
5) Elevated LDH
Thrombocytopenic Purpura (TTP) - Mechanism + Cause (3)
ADAMTS13 - Normally cleaves vWF allowing for degradation - No ADAMTS13 - No vWF degradation = over-production of micro thrombi
Causes
1) Congenital
2) Acquired - Antibodies to ADAMTS - Treat with plasmapheresis to remove the Ab
Thrombocytopenic Peurpura vs. DIC (2 Differences) vs. Hemolytic Uremic Syndrome (1 Key)
TTP vs. DIC
TTP has Normal D-Dimer (not breaking down clots causing fibrin split products)
TTP has either low ADAMST13 of Ab’s - DIC Does not
TTP vs. HUS
TTP = Worse CNS S/Sx
HUS = Worse Renal S/Sx
Hemolytic Uremic Syndrome (HUS) - Mechanism + Causes (2)
Mechanism - Microthrombi production due to endothelial damage
Acquired = E. Coli 157:H7 -Shiga Verotoxin damages endothelium Congenital/Atypical = Complement Factor H Defect (CD46 Issues)
Qualitative Platelet Disorders (2) + Mechanism
1) Bernard Souiler - Genetic GP1b deficiency - issue with platelet adhesion (can’t bind vWF
2) Glanzamann - Genetic GPIIb/IIIa deficiency - issue with platelet aggregation (can’t bind each other + form fibrin cross links)
Bernard Souiler - 2 Key Findings
1) Large Platelets with Thrombocytopenia (Platelets Die)
2) Ristocetin Test - Abnormal
Major Tests for Heme/Onc (8)
1) Nitro Blue - Chronic Granulomatous Disease
2) D-Dimer - DIC
3) Schilling Test - B12
4) Metabisulfite Test - HbS - Trait/Disease
5) Osmotic Fragility - Heriditary Spherocytosis
6) Sucrose Test - PNH + CD55 Follow-Up
7) Ristocetin Test - Benard Soulier + vWF Disease
8) Mixing Test - Lack of a Factor vs. Ab against a Factor
PT vs. PTT - Pathway Measured + Medication Checked
PT
Extrinsic = Tissue Factor/ FVII
Checks Coumadin
PTT
Intrinsic = XII, XI, IX, VIII
Checks Heparin
Hemophila A - Inheritance Pattern + Defect + Findings (4)
X-Linked Recessive VIII Deficiency
1) Normal PT with Elevated PTT
2) Hemarthrosis (Joint Bleeding)
3) Deep/Surgical Bleeding
4) FVIII binds vWF for stabliization - loss of vWF can mimic
Hemophila B - Inheritance Pattern + Defect + Findings (3)
X-Linked Recessive IX Deficiency
1) Normal PT with Elevated PTT
2) Hemarthrosis (Joint Bleeding)
3) Deep/Surgical Bleeding
Disorders of Primary vs. Secondary Hemostasis - Findings - 2 Major Differences
Primary
1) Normal PT/PTT (No Coagulation Factors Impacted) + Increased Bleeding Time
2) Typically Superficial Bleeding (Mucousal/Skin/Gums)
Secondary
1) Typically changes in either PT or PTT (Coagulation involved)
2) Typically deep bleeding - Hemarthrosis (Joint) + Surgical
Coagulation Factor Inhibitor Disease
Acquired Ab against factor - VIII and XIII Most Common
Mixing Test - Acquired Ab won’t respond to plasma infusion vs. Inherited Will
vWF Disease - Genetics + Mechanism + Findings (3)
Most Common Bleeding Disorder - Normally Autosomal Dominant
No vWf - No Adhesion - Also limited FVIII (Stabalizes)
Findings
1) Increased bleeding time with normal PT
2) PTT may or may not be elevated (FVIII)
3) Ristocetin Test
Vitamin K Deficiency - Mechanism - Affected Factors (6) + Common Causes (2)
Gamma-Carboxyglutamate Restoration of Factors
Factors - II + VII + IX + X + C + S
Impact on VII Impacts PT Most
Causes
1) Newborns
2) Long Term Antibiotics
Heparin Induced Thrombocytopenia - Mechanism + Causes (2) + Treatment + Key Point
Antibodies to Heparin Factor IV Complex
Causes - Heparin (High Risk) vs. Enoxoprin (Low Risk)
Treatment - Direct Factor X Inhibitors - E.g. Aragtroban + Lepirudin
Increases risk for Warfarin induced skin necrosis
Disseminated Intravascular Coagulation (DIC) - Mechanism + Causes (6)
Mechanism - Pathological activation of coagulation cascade - Leads to microthrombi with endothelial damage + ischemia –> Uses of platelets (bleeding)
Causes
1) Pregancy (Extra tissue thromboplastin)
2) Rattlesnake Bite
3) Sepsis (Gram -)
4) AML-M3 (with auer rods + 15/17)
5) Adenocarcinoma (Mucin actiation)
CLASS ONLY
6) Crush Injury
