Heme/Onc - Week 3 Review - Part 2 Flashcards
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
DIC Lab Findings (4) + Treatment
1) Thrombocytopenia (all platelets used up)
2) Elevated PT/PTT (factors used up)
3) Microangiopathic Anemia
4) Increased Fibrin split products + D-Dimer
Treatment - Underlying disease
Meningcoccemia - Key Points (3)
1) Cram (-) Cocci Induced Endothelial Damage + DIC
2) Waterhouse-Friderichsen Syndrome
3) Specific to adrenal cortex
Hermansky Pudlak Syndrome - Key Points (3)
1) Autosomal Recessive
2) Dense Granule Failure (Platelets)
3) Albinism + Platelet Disease
Ehlers-Danlose Syndrome - Key Points (2)
1) Collagen Defect
2) Hyper-elastic skin = adhesion issues
Sickle Cell Disease Case - Genetics + Physical Exam Findings (3) + Labs (7)
Autosomal Recessive
PE
1) Jaundice (Intravascular Hemolysis)
2) Anemia (Pale
3) Asplenia/Removed Gallbladder
Sickle Cell Disease Case - Labs (7)
Labs
1) Normocytic Anemia
2) Increased MCHC
3) Sickle Cells
4) Target Cells
5) Elevated LDH (Intravascular)
6) Elevated Platelets (Marrow trying to response)
7) Reticulocyte Count (Corrected) - Shows bone marrow responding = Hemolysis
GP6D Case - Genetics + Type of Anemia + Cause (5)
X-Linked Recessive
Normocytic Anemia with Intravascular Hemolysis
Causes - Oxidative Stress
1) Fava Beans
2) Malaria Mediaction (Primiquine)
3) DKA
4) Infection
5) Sulfamides
GP6D Case - Lab Findings (6)
1) Bite Cells
2) Heinz Bodies
3) Elevated LDH
4) Corrected Reticulocyte Count > 3%
5) Low Heptaglobin (Lots of Free Hb being bound)
6) High Bilirubin (Intravascular)
Rapid Fire Markers - CD20
Mature B-Cell
Rapid Fire Markers - CD10
ALL
Rapid Fire Markers - CD4/8
T-Cell
Rapid Fire Markers - CD103
Hairy Cell Leukemia
Rapid Fire Markers - CD34
HSC
Rapid Fire Markers - CD15
Reed Sternberg
Rapid Fire Markers - CD30
Reed Sternberg
Rapid Fire Markers - CD55
Negative = No DAF = No GPI = PNH
Rapid Fire Markers - CD46
Atypical HUS (Compliment I Issues)
Rapid Fire Markers - CD5
CLL + Mantle + T-Cell Tumors
Rapid Fire Markers - CD23
CLL (with CD5)
Solitary Meyloma - Keys (2)
1) Plasmacytoma
2) Solidatry Lesion of Bone/Soft Tissue - Monoclonal Plasma Cells
Lymphoplasmacytic Lymphoma - Keys (3)
1) Mixed Neoplastic B-Cell Plasma Tumor
2) Secretes IgM (vs. IgG in normal Multiple Myeloma)
3) Triggers Waldenstrom Macroglobulinemia (big cells are hyperciscous)
Porphyria Cutanea Targa (PCT) - Key Findings (3)
1) Funky Hands
2) Cutaneous Porphyria with photosensitivity
Congenital Erythropoietic Porphyria (CEP) - 2 Keys
1) Vampire Disease
2) Gunther’s Disease
Acute Intermittent Porphyria (AIP) - Cause + Findings (5)
Neuroviscreal Porphyria - Lack of PBD (Porphobilinogen Deaminase)
5 P’s
1) Abdominal Pain
2) Polyneuropathy
3) Port-wine urine
4) Psych S/Sx
5) Precipitated by starvation, drugs and phenotyonin
Rapid Fire Markers - CALLA - Positive (4) and Negative (4)
CD10
Positive
All B-Cell Disease - Especially ALL + Burkitt + B-Cell Lymphoma
Negative AML CLL Mantle Cell Marginal
