Hematology Flashcards
Heparin and warfarin MOA
Heparin: increases Antithrombin III levels, affects intrinsic pathway and decreases fibrinogen levels
Warfarin: inhibits vitamin K activated factors- 10, 9, 7, 2 and Protein C and S
What lab value measures heparin vs. warfarin?
Heparin: PTT
Warfarin: PT
Intrinsic pathway
XII -> XI -> IX -> VIII -> X
Factor X is where intrinsic and extrinsic collide
X -> V -> II -> XIII -> Fibrin to crosslinked fibrin
Factor II also converts fibrinogen to fibrin
Extrinsic pathway
III helps convert VII -> VIIa -> X
Antidote for heparin and warfarin
Heparin: protamine sulfate
Warfarin: Vitamin K, fresh frozen plasma
Enoxaparin MOA
Inhibits Factor X
Platelet dysfunction vs coagulation dysfunction manifestation
Platelet dysfunction: petechiae
Coagulation dysfunction: hemarthroses
Hemophilia: inheritance and types
X linked recessive A: Factor VIII dysfunction B: Factor IX dysfunction C: Factor XI dysfunction Factor VII deficiency: PT elevation only
Mixing study
Mix patient’s blood with normal blood. If the PTT corrects, it’s likely dysfunctional factors that are causing the disease. If it doesn’t, there’s an antibody present
Hemophilia characterization
Mild: >5% normal levels of factors
Moderate: 1-3% normal levels of factors
Severe: <1% normal levels of factors
Cryoprecipitate
Mainly factor VIII and fibrinogen
Small concentrations of factor XIII, vWF, and fibronectin
It is a more concentrated source of factor VIII and fibrinogen than FFP
Good for treatment of Hemophilia A (Factor VIII deficiency)
Mild hemophilia tx
DDAVP
-vasopressin is an ADH analog which increases the amount of factor VIII in the blood
von Willebrands disease inheritance
Autosomal dominant disease with low levels of vWF and Factor VIII (carried by vWF)
Diagnosis of von Willebrands disease
PT is normal. PTT and bleeding time may increase 2/2 decreased Factor VIII levels
Ristocetin cofactor assay: measures the capacity of vWF to aggregate platelets
Bernard Soulier syndrome
Deficiency of GpIb (a receptor on platelets which binds to vWF)
Glanzmann’s thrombasthenia
GP IIb/IIIa deficiency (GP IIb/IIIa is a receptor on platelets which binds to fibrinogen. The fibrinogen binds to two different receptors on different platelets, allowing platelets to aggregate)
Clopidogrel mechanism of action
Irreversibly blocks the ADP receptor
Most common thrombophilias
Thrombophilia = hypercoaguable state
Most common = Factor V Leiden
Sickle cell disease
Hereditary disease of RBCs, causing them to sickle
Sludging and occlusion of arterial vasculature can lead to stroke
-due to malformed RBCs
Tx: Exchange transfusion
-DO NOT USE FIBRINOLYTICS OR ANTI-COAGS
Antiphospholipid syndrome
Hypercoaguable state
VDRL +
Causes thrombocytopenia and prolonged PTT
Tx: LMWH or Coumadin
Lepirudin MOA
Direct thrombin inhibitor
Danaparoid (MOA)
Direct thrombin inhibitor
DIC vs TTP vs ITP MOA
DIC: deposition of fibrin in small vessels leads to thrombosis and depletion of clotting factors and platelets. Platelet microthrombi block off small blood vessels
TTP: Platelet microthrombi block off small blood vessels
ITP: IgG antibodies against patient’s platelets are formed and destroy platelets. NO MICROTHROMBI PRESENT
DIC associated disorders
Sepsis, acidosis, drug reactions, massive trauma, ARDS, intravascular hemolysis
OB complications
Neoplasms, APML
DIC vs liver disease
DIC: Factor VIII is depleted also, while in liver disease factor VIII is normal (because Factor VIII is made by endothelial cells)
DIC Tx
Reverse underlying cause, RBC and platelet transfusion
Microangiopathic hemolytic anemia
Caused by DIC, TTP, and HUS
Basically, small microthrombi of platelets deposit in small blood vessels and RBCs shear when they go through them
Causes hemolysis and fragmented RBCs (schistocytes)
5 common symptoms of TTP
TTP = idiopathic activation of platelets leading to microthrombi and microangiopathic hemolytic anemia. TTP definition is MAHA + end-organ ischemia 5 common si/sx: -thrombocytopenia -MAHA -neuro changes (delirium, sz, stroke) -impaired renal function -fever
TTP vs HUS
HUS occurs after an E Coli infection
Both = MAHA + end-organ damage
HUS has much worse renal failure
Treatment of TTP
Steroids to decrease microthrombus formation
Plasmapharesis
DO NOT REPLACE PLATELETS
ITP
IgG antibodies against patient’s platelets causes thrombocytopenia
BM production of platelets increases (increased megakaryocytes in the BM)
Sx: mild, no systemic sx; some bruising, petechiae, hematuria, hematemesis, melena
ITP associated with what diseases:
lymphoma, leukemia, SLE, HIV, HCV
Most common pediatric cause of renal failure
HUS
Treatment of ITP
Most cases remit (in childhood)
Symptomatic bleeding: corticosteroids, high dose IVIG, and splenectomy
-PLATELET TRANSFUSION IS NOT HELPFUL
Differential diagnosis for thrombocytopenia
HIT SHOC: HIT/HUS ITP TTP/Treatment (ie meds) Splenomegaly Hereditary (ie Wiskott Aldrich syndrome) Other causes ie malignancy Chemotherapy
What are bands on a differential?
Bands = precursor to neutophils, eosinophils, basophils
Retic > 2.5
Hemolysis or hemorrhage
What type of anemia is pyridoxine deficiency?
Can cause sideroblastic anemia if INH is given without pyridoxine (microcytic or normocytic)
Physical exam findings of Fe deficiency anemia
Glossitis, angular cheilitis, and koilonychia (spoon nails)
Fe deficiency vs ACD labs
Fe deficiency:
- Serum Fe: decreased
- Ferritin: decreased
- Transferrin/TIBC: increased
- serum transferrin receptor: increased
ACD:
- Serum Fe: decreased
- TIBC/transferrin: decreased
- ferritin: increased
- serum transferrin receptor: normal
Acquired sideroblastic anemia
Defective heme synthesis 2/2 pyridoxine dependent impairment ie INH
Dimorphic RBCs: both hypochromic and monochromic
Tx: B6
Labs: normal Fe, decreased TIBC
Cobalamin
B12
What cells produce intrinsic factor?
Parietal cells in the GI tract
Folate stores length vs. B12
Folate: 4 months
B12: years
B12 deficiency: sx other than anemia
Neuro sx: deymyelinating disorder causing motor, sensory, autonomic, and/or neuropsychiatric dysfunction
-aka subacute combined degeneration of the cord
What infection can cause B12 deficiency?
Diphyllobothrium latum: tapeworm
Schilling test
Ingestion of radiolabeled cobalamin:
- First give pt unlabeled B12 IM to saturate all B12 receptors in the liver
- Then give an oral challenge of radiolabeled B12. If everything is normal, the B12 will be absorbed in the GI tract, but the liver is unable to use it so it should pass through into the urine. Radiolabeled B12 in the urine = positive test, meaning that pt has nutritional B12 deficiency
- No radiolabeled B12 in the urine means pt may have pernicious anemia, bacterial overgrowth, or pancreatic enzyme deficiency; give B12 with IF and check urine, with antibiotics and check urine, and with pancreatic enzymes and check urine
Diagnosis of B12 and folate deficiency
B12: elevated MMA and homocysteine, increased LDH
Folate: normal MMA, elevated homocysteine, normal LDH
G6PD deficiency
X-linked recessive hemolytic anemia
Increased sensitivity to oxidative stress
Paroxysmal nocturnal hemoglobinuria
Hemolytic anemia
Increased blood cell sensitivity to complement activation
Patients are prone to thrombotic events
Hereditary spherocytosis
-what is it, how to diagnose, what to supplement these patients with
Abnormality of the RBC membrane, leading to spherocytes on smear which lack areas of central pallor
Dx: with a osmotic fragility test (these RBCs are more fragile)
Supplement with folate
Autoimmune RBC destruction
2/2 EBC, mycoplasma, CLL, rheumatoid disease, or medications
How does hemolytic anemia present differently than anemia?
Jaundice, low haptoglobin, elevated indirect bilirubin, elevated LDH
Urine is dark with hemoglobinuria
Increased excretion of urinary and fecal urobilinogen
Elevated retic count
G6PD stressors
Infection, quinidine, nitrofurantoin, fava beans, antimalarials, dapsone, sulfonamides, metabolic acidosis
Coombs test
Direct: Pt’s RBCs are washed to remove any unbound antibodies and mixed with antihuman antibodies (aka Coombs reagent); the antihuman antibodies bind the pt’s anti-RBC antibodies on multiple RBCs and cause agglutination = + test
Indirect: Patient’s serum is collected (which contains anti-RBC antibodies) and mixed with donor RBCs; The donor RBCs will bind to the pt’s antibodies; Antihuman antibodies are added (Coombs reagent) and these will agglutinate the mixture already
the big difference is where the RBCs are from
Causes of aplastic anemia
Fanconi’s anemia (congenital), Parvovirus B19, HIV, toxins (drugs, cleaning solvents), and radiation
Aplastic anemia: hx/PE, Dx, Tx
Hx/PE:
-pancytopenia: pallor, weakness, tendency to infection, petechiae, bruising, bleeding
Dx: BM biopsy shows hypocellularity and space occupied by fat
Tx: blood transfusion + stem cell transplant
- immunosuppresion with cyclosporine A and antithymocyte globulin
- infections are major cause of mortality
Fanconi’s anemia
Hereditary aplastic anemia
PE: cafe au lait spots, short stature, radial/thumb hypoplasia/aplasia
Sickle Cell Disease
-genetics and affected protein
Genetics: autosomal recessive disorder
Affected protein: B chain of hemoglobin
Symptoms of sickle cell disease
Dactylitis, cholelithiasis, increased cardiac output (cardiomegaly and murmur), delayed growth, splenic infarction (predisposes to pneumococcal sepsis), acute chest syndrome (pneumonia and pulmonary infarct), pain crises (triggers: cold temp, dehydration, infection)
Osteomyelitis in sickle cell disease
Most common: S aureus
Very prone to Salmonella also
Increased risk of AVN of the hipt
Target cells
sickle cell disease
Treatment of sickle cell disease
Hydroxyurea, which stimulates fetal hemoglobin production
Treatment of vaso-occlusive reactions in sickle cell disease
Pain management, aggressive hydration, incentive spirometry, and keeping sickle cell variant < 40%
-this will keep VOD from progressing to acute chest syndrome
Alpha vs beta thalassemia
Alpha: affects one or more of 4 alpha-globin chains
Beta: affects one or both of 2 beta-globin chains
Types of thalassemia
B-thal major: absent both B-globin genes; severe microcytic anemia and need chronic transfusions or marrow transplant
B-thal minor: 1 of 2 B-globin genes; asymptomatic, but cells are microcytic and hypochromic
Hydrops fetalis: 0/4 alpha-chains; patients die in utero
Hemoglobin H disease: 1/4 alpha chains present; severe hypochromic, microctyic anemia; chronic hemolysis, splenomegaly, jaundice, and cholelithiasis; elevated reticulocyte count
a-thal trait: 2/4 alpha chains; low MCV, but asymptomatic
Silent carrier: 3/4 alpha chains present; no signs or symptoms of dz
Fe chelator
Deferoxamine
Hyperviscosity syndrome
2/2 erythrocytosis
Easy bruising/bleeding, blurred vision, pruritis after a warm bath, hsm, CHF, neuro abnormalities
Causes of primary erythrocytosis
Polycythemia vera, hypoxia (smoking, high altitudes, restrictive lung dz, fetal hypoxia), tumors (EPO producing tumor)
PCV pathophysiology
Clonal proliferation of a pluripoitent marrow stem cell 2/2 JAK2 mutation; all marrow lines increase, RBCs more than others
Low EPO levels
Polycythemia vera treatment
Cytoreductive drugs: hydroxyurea, interferon
-ASA also because PCV is prothrombotic
Types of blood transfusion reactions
Nonhemolytic febrile reaction
Minor allergic reaction
Hemolytic transfusion reaction
Nonhemolytic febrile reaction
Cytokine formation during storage of blood
Fevers, chills, rigors, malaise 1-6 hours after transfusion
Stop transfusion and give acetaminophen
Minor allergic reaction to blood transfusion
Antibody formation against donor proteins, after receiving plasma containing product
p/w prominent urticaria
Tx: antihistamines; if the reaction is severe, may need to stop and give epinephrine
Hemolytic transfusion reaction
Antibody formation against donor erythrocytes, results from ABO incompatibility or from minor Ag mismatch
p/w fevers, chills, nausea, flushing, burning at IV site, tachycardia, hypotension shortly after transfusion; can cause hemoglobinuria which can lead to ATN and renal failure
Tx: stop transfusion immediately; give IVF and maintain UO
Leukocyte alkaline phosphatase
Increased in leukemoid reactions
Decreased in hematologic malignancies
Porphyria
Congenital abnormality of heme production which leads to accumulation of porphyrins
Photodermatitis
Neruopsychiatric complaints
Visceral complaints: usually colicky abdominal pain and seizures
PE: tachycardia, skin erythema and blisters, areflexia, and nonspecific abdominal exam
Erythropoietic porphyria: hemolytic anemia
Porphyria triggers
EtOH, OCPs, barbiturates
Pink urine
porphyria
