Hematology Flashcards
Causes of microcytic anemia (MCV less than 80)
Iron deficiency lead poisoning sideroblastic thalassemia anemia of chronic disease
Causes of normocytic anemia (MCV 80-100)
anemia of chronic disease
hemolytic anemia
hemorrhagic anemia
Causes of microcytic anemia (MCV >100)
Folate deficiency
B12 deficiency
Liver disease
etOH abuse
Iron deficiency anemia
MC overall
Etiology: chronic blood loss (MC), inadequate iron intake, poor iron absorption, pregnancy
Presentation: Fatigue SOB, exercise intolerance, tachypnea Tachycardia - d/t decreased O2 carrying capacity Pallor - conjunctivae, nail beds, palms Ice pica Restless legs syndrome Angular stomatitis (chelitis) Spooning of nails
Dx: Low Hgb and Hct Low MCV Low MCH and MCHC - hypochromic Iron: low iron, low ferritin, high transferrin, low %TIBC
Tx: iron supplements, determine underlying cause
Lead poisoning
Etiology:
Adult - occupation lead exposure
Child - ingestion of dust from lead-based house paint
Presentation:
microcytic anemia -> fatigue, dyspnea, pallor -interferes with heme synthesis
Abd pain and constipation
Joint and muscle pain
HA, irritability, short term memory loss - AMS, neuropathy
Peripheral neuropathy - foot drop, wrist drop
Gingival “lead lines”
Dx:
Low Hgb and Hct, low MCV
High serum lead level
Smear: basophilic stippling - blue
Tx: Eliminate source of exposure Chelation for severe poisoning Adults - EDTA or succimer (DMSA) Children - add dimercaprol
Sideroblastic anemia
Etiologies:
Inherited - defect in heme synthesis pathway
Acquired - etOH abuse, isoniazid (low B6), Zn or Cu toxicity
Presentation:
Microcytic anemia - fatigue, dyspnea, pallor
Dx:
Low Hgb and Hct, low MCV
Bone marrow bx - ringed sideroblasts - nucleated RBC precursors with iron granules encircling the nucleus - blue
Tx: Inherited - vit B6 - pyridoxine Acquired - addressed underlying cause RBC transfusion, epo Chelation - deferoxamine or phlebotomy prn for iron overload
Conditions that shift Hgb-O2 dissociation curve left
Holds onto O2 tightly
Alkalosis low temp low CO2 low 2,3-DPG Hgb F (binds less 2,3-DPG)
Conditions that shift Hgb-O2 dissociation curve right
unloads O2
acidosis high temp High altitude exercise elevated CO2 high 2,3-DPG
Alpha thalassemia
Defect in alpha globin production
MC in African and Asian descent
1 defective allele - minima; asx
2 defective alleles - minor; MC; minimal microcytic anemia
3 defective alleles - Hemoglobin H dz; 4 beta globins, microcytic anemia, chronic hemolysis
4 defective alleles - hydrops fetalis; Hgb Bart’s -4 gamma globins very far left shift of Hgb O2 curve; -> fetal edema and intrauterine death
Beta thalassemia
Defect in beta globin production
MC in Mediterranean descent
1 defective allele - minor; low beta globin, high Hgb A2 (alpha 2, delta 2), minimal anemia “trait”
2 defective alleles - major; absent beta globin; Hgb F (alpha 2 gamma 2) + Hgb A2; severe anemia
Dx and Tx of thalasemias
Dx: \+/- microcytic anemia Normal iron studies Smear: atypical RBC forms - target cells Hemoglobin electrophoresis to confirm
Tx:
Transfusion -> iron overload -> iron chelation (deferoxamine)
Always r/o thalassemia in all microcytic anemia to avoid iron overload
Sickle cell disease
Glu->Val position 6 of Beta globin gene on Chr 11
AR
Heterozygous - trait = asx
Homozygous - disease - form Hgb S
Presentation:
Acidosis, hypoxia, or dehydration -> sickling -> hemolysis and vasooclusion/infarction
Episodes of acute pain - sickle crisis
-triggered by dehydration, infection, hypoxia, trauma, illness
Acute chest syndrome
Stroke
Dactylitis - sickling in fingers
Bone infarction; osteonecrosis of humeral or femoral head
Priapism
Splenic sequestration crisis -> splenic infarcts -> autoinfarct by 3-4 yo
-risk of infection by encapsulated bacteria (S. pneumo, H. flu, N. meningitides)
Salmonella osteomyelitis
Parvovirus B19 -> aplastic anemia/crisis
Dx:
Anemia
Smear: sicking of RBCs
Hgb electrophoresis: Hgb S + increased Hgb F
-baby has high Hgb F - asx first 3 mo of life
Skull Xr: “hair on end” appearance from marrow hyperplasia
Tx:
IVF, supplemental O2, opioids during acute pain episodes
Folic acid to optimize marrow production of RBCs
Hydroxyurea to increased Hgb F production
Immunize - pneumococcal, HIB, meningococcal, influenza
ppx PCN until 5 to prevent pneumococcal infection
General features of hemolytic anemia
Presentation:
- fatigue, dyspnea, tachypnea, tachycardia
- Pallor and or jaundice (depending on the type of analysis)
Diagnostic testing for hemolytic anemia
low hemoglobin and hematocrit Normal MCV Elevated indirect bilirubin Elevated LDH Serum haptoglobin low Elevated reticulocyte count Peripheral smear may show should schistocytes, spherocytes, sickle cells, etc
Causes of intrinsic hemolysis
Problem inside RBC
Membrane defects
Enzyme deficiencies
Hemoglobinopathies
Extrinsic hemolysis causes
Microangiopathic anemia
- mechanical destruction of RBCs passing through a obstructed or narrowed small vessels
- examples: DIC or TTP-HUS
- peripheral smear show schistocytes
Macroangiopathic anemia
- mechanical destruction of RBCs due to mechanical forces in large vessels
- examples: prosthetic valves, aortic stenosis
RBC infections - malaria, babesiosis
Autoimmune hemolysis - Ab-mediated
Autoimmune hemolytic anemia - cold agglutinins
Antibodies against RBCs the interact more strongly at low temperatures (4C)
Nearly always IgM
After regularly and infections with EBV or Mycoplasma and some malignancies such as CLL
Circulation to a cold extremity leads to IgM find RBC antigen -> complement fixation -> RBC lysis
Autoimmune hemolytic anemia - warm agglutinins
Antibodies react against RBC antigens at body temperature
Nearly always IgG
Seen in SLE, CLL and non-Hodgkin’s lymphoma malignancies, HIV or EBV, congenital immune abnormalities
Autoimmune hemolytic anemia - drug induced
Drugs induced IgG antibodies that can crossreact with RBCs: Cephalosporins Penicillin Quinidine or quinine NSAIDs Methyldopa
Coombs test
RBC agglutination with the addition of anti-human antibody because RBCs are coated with immunoglobulin or complement proteins
Direct Coombs (DAT) -prepared antibodies are added to a patient RBCs to detect the presence of immunoglobulins already present on the RBCs (using antibody to detect antibody that is already bound)
Indirect Coombs
- patient serum is incubated with normal RBCs to detect the presence of antibodies
- positive when antibodies to foreign RBCs are present - used to test blood prior to transfusion and to screen for maternal antibodies to fetus’ blood
Treatment of autoimmune hemolytic anemia
Warm agglutinins - glucocorticoids, rituximab (against B cells), splenectomy
Cold agglutinins - avoid exposure to cold temperatures
Drug-induced antibodies- stop offending drug
Hereditary spherocytosis
Genetic effect of the red cell membranes and cytoskeleton -> spherical RBCs, no central pallor
Presentation:
Splenomegaly
Hemolysis -> jaundice +/- gallstones
Aplastic anemia following Parvovirus B19 infection
Diagnostic testing:
- anemia with reticulocytosis and increased MCHC
- peripheral smear - spherocytes
- higher incidence of pseudohyperkalemia (rbc’s lyse after blood draw)
- positive osmotic fragility test - rbc’s lyse readily in a hypotonic saline solution
Treatment
Folic acid 1 mg per day
RBC transfusions in cases of extreme anemia
Splenectomy in moderately severe disease -> Howell-Jolly body when no spleen
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
X linked recessive
G6PD is it essential for RBCs to repair oxidative damage - maintains normal glutathione levels
Presentation
hemolysis occurs 2-4 days following ingestion drugs/foods:
“Spleen Purges Nasty Inclusions From Damaged Cells”
-sulfonamides
-Primaquine
-nitrofurantoin
-isoniazid
-fava beans
-dapsone
-Chloroquine
Fatigue, jaundice, dark urine, back or abdominal pain
Diagnostic testing:
Peripheral smear:
-Heinz body - precipitation of oxidized hemoglobin within RBCs
-Degmacytes (“ bite cells”) - deformed RBCs following removal of clients bodies by splenic macrophages
Management - avoid oxidants
Pyruvate kinase deficiency
RBCs require pyruvate kinase to perform glycolysis
-can’t make ATP, can’t regulate homeostasis without Na/K ATPase activity -> swell and lyse
Presentation
-mild chronic anemia to severe neonatal hemolytic anemia -> jaundice and splenomegaly
Diagnostic testing
- pyruvate kinase activity
- genetic testing
Management
RBC transfusions
Splenectomy
Transfusion reaction occurring during transfusion, mild
urtricarial reaction:
-during transfusion
Cause: IgE antibodies against soluble antigens in donor plasma
Findings - urticaria
Treatment - diphenhydramine - if resolves continue transfusion
Transfusion reaction occurring seconds to minutes after starting transfusion
Anaphylactic reaction:
Occurs seconds to minutes after starting transfusion
Cause: possibly anti-IgA IgG antibodies in patients with IgA deficiency
Findings: shock/hypertension, angioedema, respiratory failure
Treatment - epinephrine, IVF, O2, +/- intubation
Transfusion reactions occurring 1 to 6 hours after transfusion
Nonhemolytic febrile reaction
occurs one to six hours after transfusion
Cause: cytokines produced by store donor cells
Findings: fever, chills, malaise
Treatment: acetaminophen
Transfusion reactions occurring during transfusion - severe
Acute hemolytic reaction
Occurs during transfusion
Cause: ABO incompatibility - clerical error
Findings: severe hemolysis, fever, chills, tachycardia, tachypnea, hypotension
Treatment: aggressive supportive care
Transfusion reactions occurring 2 to 10 days after transfusion
Delayed hemolytic reaction
Occurs 2 to 10 days after transfusion
Cause:: anti-Kidd or anti-D (Rh) antibodies
Findings: mild fever, hemolysis, increased indirect bilirubin
Treatment: no therapy needed
Anemia of chronic disease
Etiology: singing chronic inflammatory states, disorder of iron mobilization and utilization
Presentation: signs and symptoms of anemia (fatigue, pallor, dyspnea)
-often asymptomatic
Diagnostic testing:
Mild normocytic or microcytic anemia
Iron studies: low serum iron, elevated/normal ferritin, low normal transferrin, normal % transferrin saturation
Management:
Treatment of the underlying disorder
+/- erythropoietin supplements
Aplastic anemia
pancytopenia resulting from bone marrow failure
Etiologies:
- radiation
- drugs (chemo, chloramphenicol, sulfonamides, phenytoin)
- viral infections - Parvovirus B19, HIV, hepatitis viruses
- toxins - industrial chemicals, insecticides
- congenital
Presentation:
- anemia (weakness, pallor, fatigue)
- leukopenia (persistent infections)
- thrombocytopenia (easy bruising, petechiae)
Diagnostic testing:
- anemia, leukopenia, thrombocytopenia
- bone marrow biopsy - hypocellularity and fatty infiltration, r/o leukemia or metastatic cancer infiltrating marrow
Management:
- Address the underlying cause
- BM transplant
- patients with no suitable match (or mild anemia) maybe treated with immunosuppressants
B12 deficiency causes
pernicious anemia - autoantibodies against gastric parental cells or intrinsic factor
chronic gastritis -> impaired intrinsic factor production and gastric acid excretion
Malabsorption - Crohn’s, pancreatic disease
Gastrointestinal bypass/resection -> bacterial overgrowth in blind loop of jejunum
Resection of terminal ileum - Side of absorption of IF-B12 complex
Diphyllobothrium latum infection - Fish tapeworm - Japan
Inadequate B12 intake - strict vegans
Presentation of B12 deficiency, diagnostic testing, management
S/S of anemia - fatigue, pallor, dyspnea
Neurological problems
-subacute combined degeneration - loss of vibration sense and proprioception, weakness/paresthesias/ataxia in the lower extremities
-dementia
Atrophic glossitis - inflammation the tongue, loss of papillae -> smooth (also in folate/iron def)
Diagnostic testing:
Megaloblastic anemia - macroovalocytes + hyper segmented neutrophils
Low serum B12 level
Elevated METHYLMALONIC ACID (MMA) and homocystine
Schilling test
Anti-IF antibodies - pernicious anemia
Management
- IM B12
- high dose oral B12 supplements
- B12 nasal spray
B9 (folate) Will improve anemia but not neurologic symptoms
Folate deficiency (B9)
Inadequate folate intake - alcoholism, elderly, poor nutrition
S/S of anemia - fatigue, pallor, dyspnea
Atrophic glossitis
No neurologic defects
Diagnostic testing:
Megaloblastic anemia -macroovalocytes + hyper segmented neutrophils
Low serum folate level and RBC folate level
Normal methylmalonic acid
Elevated homocysteine
Management:
Oral folate supplements
Be sure to evaluate for concomitant B12 deficiency
Findings of thrombocytopenia
Micro hemorrhages:
- epistaxis
- mucosal bleeding
- bruising
- petechia
- Purpura
Labs
-platelet count less than 150,000
Prolonged bleeding time (platelet plug)
PT and PTT normal (fibrin clot)
von Willebrand disease
AD deficiency of vWF +/- factor VIII
vWF: released by an injured vascular endothelial cells, enables platelet adhesion and aggregation
-stabilizes factor VIII
Presentation:
Easy bruising, mucosal bleeding, skin bleeding, menorrhagia
Diagnostic testing Elevated PTT - Factor VIII Elevated bleeding time Normal platelet count vWF antigen low Plasma vWF activity (ristocetin cofactor activity) low Factor VIII activity low or normal
Management:
Desmopressin (DDAVP) - increases vWF release - first line for acute bleeding
-vWF concentrate for severe/refractory bleeding or before surgery
-oCP’s for menorrhagia
-avoid aspirin and other platelet inhibitors
Hemophilia
X linked R
- A: factor VIII
- B: factor IX
Presentation: Hemarthrosis Hematuria G.I. bleeding Intracranial hemorrhage is a rare Mucosal bleeding, epistaxis Bleeding following minor trauma or procedures
Diagnostic testing: Elevated PTT Normal PT Normal bleeding time and platelet count Factor VIII and factor IX activity levels Genetic testing
Management:
A: give factor VIII
B: give factor IX
DDAVP Will increase factor VIII levels - A
Vitamin K deficiency
Required for factors X, IX, VII, II, protein C, S
-protein C and S inactivate factors V and VIII
Causes of efficiency
- neonates
- antibiotic use eradicate flora
- malabsorption - pancreatic insufficiency, celiac disease, IBD
Presentation:
Easy bruising, mucosal bleeding, melena, hematuria
Hemorrhagic disease of newborn -> intracranial hemorrhages
Diagnostic testing:
Elevated PT and INR
Normal or elevated PTT
Management
- vitamin K oral or IM
- acute bleeding - FFP
Disseminated intravascular coagulation (DIC)
Widespread pathologic intravascular coagulation -> consumption of platelets and coagulation factors-> hypocoagulability
Causes: Sepsis Trauma and extensive surgery OB complications - amniotic fluid embolism or placental abruption Pancreatitis Malignancy Transfusions
Presentation: Bleeding from wounds/surgical sites hemoptysis Venus or arterial thrombosis -> organ ischemia Hypotension Jaundice Cyanosis a distal extremities
Diagnostic testing
Low platelets
Elevated bleeding time
Elevated PT and PTT
Low fibrinogen
Elevated fiber and split products and the and D dimer
Hemolysis-> schistocytes, anemia, elevated bilirubin, low haptoglobin, elevated LDH
Management:
Treat underlying problem
Aggressive supportive care
Treat acute bleeding with platelet transfusions, FFP, +/- RBC transfusion
inherited hypercoagulable states
Factor V Leiden mutation - MC Prothormbin 20210 gene mutation - stays around longer Antithrombin deficiency Protein C deficiency Protein S deficiency
SIRS
dysregulated inflammatory response without infectious causes
Seen in: Pancreatitis acute adrenal insufficiency Autoimmune disease Vasculitis PE Severe trauma Severe burns Fat embolic syndrome
Sepsis definition
Life-threatening organ dysfunction - dysregulated Post response to infection
Increase in Sequential Organ Failure Assessment (SOFA) of two or more points:
- CNS (Glasgow coma score)
- CV (amount of vasoactive meds required to maintain MAP)
- renal (serum creatinine or urine output)
- coagulation (platelet count)
- hepatic (serum bilirubin level)
- Respiratory (PaO2:FiO2 ratio)
Infections known to cause sepsis
Sinusitis Pneumonia Peritonitis Endocarditis cholangitis Pancreatic infection Septic arthritis UTI Catheter related bacteremia
Most common organisms: Staph spp, esp MRSA Strep spp. N. Meningitidis E. coli Klebsiella pneumoniae Pseudomonas aeruginosa Candida spp. (treat with ampotericin B)
Treatment of sepsis
Airway and breathing: O2, monitor pulse ox, secure airway
Circulation: -indicators of adequate perfusion: BP Temperature of the extremities Urine output and renal function Serum lactate level
Treatment of hypertension:
IVF - NS or LR
Vasopressor - norepi
IV glucocorticoids - adrenal insufficiency
Identify and treat underlying infection:
- blood/urine/sputum cultures
- CXR
- Cx surgical incision
- Cx catheters
- Broad spectrum IV antibiotics
Insulin to maintain glucose 140-180
Most common parasite that causes malaria
Plasmodium vivax
Pasmodium falciparum
Most dangerous parasite that causes of malaria
Plasmodium falciparum (CNS problems)
Signs and symptoms associated with malaria, diagnostic steps
Periodic fever at 1-3 day intervals Diaphoresis Headache Arthralgias Myalgias abdominal pain Vomiting Diarrhea Encephalopathy - P. falciparum Reliance efficiency Pulmonary edema
Dx:
Peripheral smear - Banana shaped gametocyte
Antigen testing
PCR
Malaria endemic areas
Sub-Saharan Africa
Central and South America
Asia - india, Indonesia, Laos, cambodia, china, Korea, Vietnam
Myeloid leukemia
Proliferation myeloid cells - precursors of rbc’s, platelets, granulocytes
lymphocytic leukemia
Proliferation of lymphoid cells - precursors of lymphocytes
Acute leukemia
Proliferation of immature “blast” cells in and the bone marrow and peripheral blood
Chronic leukemia
Proliferation of mature cells
Acute lymphocytic leukemia (ALL)
Children ages 2-5
Whites and Latinos > blacks
Down Sn “ALL fall DOWN”
Presentation: Bone pain Fever Lymphadenopathy Fatigue Recurrent infections
Dx:
lymphoblasts - PAS+, TdT+
Anemia
Thrombocytopenia
Tx:
Chemo: vincristine + steroids
Acute myeloid leukemia (AML)
Adults median age 65
M>F
M0-M7
M3- acute promyelocytic AML (auer rods)
Presentation:
Fatigue
Easy bruising
Recurrent infections
Dx: Pancytopenia Myeloblasts: - myeloperoxidase (MPO)+ -Auer rods (thin red/pink rods in cytoplasm) - M3
Tx: chemo
Chronic myeloid leukemia (CML)
Adult median age 50
Exposure to radiation
Philadelphia chromosome t(9;22), bcr-abl (tyrosine kinase)
“Philadelphia CreaML cheese”
Presentation: Indolent course -fatigue, splenomegaly, bleeding Blast crisis - >20% blasts in BM and peripheral blood -rapidly fatal
Dx:
Anemia
Thrombocytosis - 500-700K
Leukocytosis - 100K
Tx: Hematopoietic cell transplant Tyrosine kinase inhibitor -imantinib -dasatinib -Nilotinib
Chronic lymphocytic leukemia (CLL)
Elderly adults 70-80s
Presentation: Most asx Fever Night sweats Fatigue Lymphadenopathy Hepatosplenomegaly
Dx:
Severe leukocytosis >70
“Smudge cells” on smear
Tx:
Periodic monitoring
Chemo/rad prn
Myelodysplastic syndromes
Dysplasia of myeloid cells, may progress to leukemia -> AML
Risk factors:
Age >65
Associated with exposure to chemo, radiation, or benzene
Presentation: Often asx Anemia -> fatigue Neutropenia -> bacterial infections Thrombocytopenia -> petechiae and purpura
Dx:
CBC: macrocytic anemia, neutropenia (hypogranular granulocytes), thormbocytopenia
Peripheral smear: pseudo Pelger-Huet anomaly - neutrophils with 2 nuclear lobs connected by thin strand
BM bx: dysplasia and disordered hematopoiesis
Tx:
Monitored for progression
Transfusions and growth factors as needed
Hematopoietic cell transplant
