Overview of Hematology

1
Overview of Hematology

• Brandon West, PA-C
• E-mail bdwpac_at_gmail.com

2
Introduction and Objectives

• Hematology
• Study of normal and pathologic aspects of blood
• Be familiar with concepts essential for practice
  of primary care medicine
• Understand and interpret complete blood count
  (CBC) reports
• Recognize common blood disorders and know when to
  request hematology consultation
• Ace your examination

3
Topics

• Hematopoiesis
• Complete blood count (CBC)
• Anemia
• Polycythemia
• Leukopenia
• Leukemia and lymphoma
• Myeloma
• Coagulation
• Transfusion
• Case studies
• Ask questions at any time!

4
Blood

• Suspension of cells in a solute of water,
  proteins, and electrolytes
• Average volume is 5 liters
• 70mL per kg body weight
• Plasma
• Blood from which the cellular components (RBCs,
  WBCs, platelets) have been removed by centrifuge
• Color is yellow
• Contains coagulation proteins (clotting factors)

5
Hematopoiesis

• Development of blood cells and other formed
  elements
• Sites vary throughout development
• Fetal yolk sac, liver, spleen
• Pediatric axial and appendicular skeleton
• Adult axial skeleton (sternum and pelvis)
• Stem cells
• Primitive self-replicate and differentiate to
  become increasingly specialized progenitor cells
  which form mature cells
• Process regulated by growth factors
  (interleukins, erythropoietin, thrombopoietin,
  G-CSF)
• Early lineage division between progenitors for
  lymphoid and myeloid cells

6
Hematopoiesis
7
Complete Blood Count

• White blood cells (WBC)
• Differential
• Neutrophils, lymphocytes, monocytes, eosinophils,
  basophils, bands
• Must specify whether to include when ordering
  study
• Red blood cells (RBC, Hgb, Hct)
• Platelets (PLT)
• Mean corpuscular volume (MCV)
• Red cell distribution width (RDW)

8
Red Blood Cells

• Transport oxygen via hemoglobin from lungs to
  peripheral tissues and organs
• Normal lifespan 120 days
• Reticulocytes
• Immature red blood cells
• Calculating proportion within circulation assists
  in determining cause of anemia
• Normal is 1-2
• Low suggests decreased production (i.e.
  nutritional or marrow problem)
• High suggests bleeding or premature destruction
  of red blood cells (i.e. hemolysis)

9
Red Blood Cells

• Peripheral blood smear
• Normal

10
Red Blood Cells

• Erythropoietin (EPO)
• Growth factor produced by kidneys that is
  essential for RBC production and release
• Sense tissue oxygen content
• EPO increases when oxygen delivery to kidneys
  falls in setting of anemia and hypoxemia
• Response is blunted or absent in patients with
  kidney disease
• Recombinant formulations commercially available
• Procrit and Aranesp
• Specific indications
• Black box warning

11
Anemia

• Defined by measurement of hemoglobin
  concentration
• Normal 15 in males 14 in females
• Patients are anemic when hgb is gt 2 standard
  deviations below normal
• Determining reticulocyte count and MCV are first
  steps in determining etiology
• Almost 1/3 of the world population is anemic!

12
Anemia

• Manifestations related to duration and severity
  of anemia
• May provide important clues as to etiology
• Body has physiologic responses to chronic anemia
  such that many patients are asymptomatic until
  hgb lt 8 g/dL
• Fatigue, pallor, dyspnea, dizziness, dyspnea on
  exertion, ischemic pain, cognitive abnormalities
• Symptoms and signs of acute blood loss
  (hemorrhage) are related to hypovolemia
• Hypotension, tachycardia, palpitations,
  orthostasis, syncope, shock

13
Anemia

• Mechanisms
• Blood loss / hemorrhage
• Initial focus in ALL anemic patients
• Gastrointestinal tract, menstruation
• Hemolysis
• Shortened RBC survival time not explained by
  bleeding
• Details later
• Decreased production (hypoproliferative)
• Nutritional deficiency (iron, B12, and folate)
• Systemic illness (CKD, cancer, rheumatologic
  disease, etc.)
• Bone marrow disorders

14
Microcytic Anemia

• Microcytosis small cells (MCV lt80)
• Most common type of anemia encountered in primary
  care
• Differential diagnosis
• Hemoglobinopathy (inherited)
• Iron deficiency
• Chronic disease (may also be normocytic)
• Inflammation
• Lead poisoning
• Check iron studies for clarification
• Be familiar with interpretation (see next slide)

15
Microcytic Anemia

• Peripheral blood smear
• Microcytosis, Hypochromic

16
Microcytic Anemia
RDW is often elevated in iron deficiency anemia
look for this along with low MCV on CBC report
17
Iron Deficiency

• Most common cause of anemia
• Etiology
• Slow depletion of stores through bleeding
• Consider colorectal cancer (FOBT, colonoscopy?)
• Poor dietary intake
• Poor absorption
• Pregnancy
• Key symptoms and signs
• Pica
• Management
• Oral replacement requires 3-6 months of therapy
• Ferrous sulfate (OTC), ferrous gluconate
  (Niferex)
• If no response or poor tolerance, consider
  intravenous replacement and refer to hematology
• Iron dextran (Infed)

18
Macrocytic Anemia

• Macrocytosis large cells (MCV gt100)
• Differential diagnosis
• B12 deficiency
• Pernicious anemia
• Folate deficiency
• ETOH
• Medication
• Check vitamin B12, RBC folate, fasting
  homocysteine, and methylmalonic acid (MMA)
• HC and MMA are elevated in subclinical B12 and
  folate deficiency

19
Vitamin B12 Deficiency

• Vegans, bariatric surgery patients, and patients
  with inflammatory bowel disease
• May be related to lack of intrinsic factor which
  is required for B12 absorption in small bowel
• Pernicious anemia (autoimmune)
• Key symptoms and signs
• Neuropathy
• Glossitis
• Dizziness
• Hair loss
• Dementia
• Management
• Oral replacement not effective
• Cyanocobalamin 1000 mcg IM weekly x 4, then
  monthly (lifelong)
• Nasal spray now available

20
Folate Deficiency

• Common in alcoholics
• Management
• Folic acid 1 mg po daily
• Repeat fasting HC after 3 months if still
  elevated, may increase folic acid to 2 mg daily

21
Hemolytic Anemia

• History and physical findings
• Review of PMH, FH, and medications
• Jaundice is common
• Occasional LUQ abdominal discomfort
  (splenomegaly)
• Lab findings
• Elevated reticulocyte count
• Reflects bone marrow compensating for peripheral
  RBC destruction
• Elevated LDH
• Elevated total bilirubin (indirect/unconjugated)
• Decreased haptoglobin
• Abnormal cells on peripheral blood smear
  examination

22
Hemolytic Anemia

• Congenital
• Membrane defects
• Hereditary spherocytosis
• Clinical picture variable splenomegaly and
  pigment gallstones common often well-compensated
  anemia
• Spherocytes seen on peripheral smear
• Osmotic fragility test
• Splenectomy is curative
• Hereditary elliptocytosis
• Enzyme defects
• G6PD deficiency
• Affects 10 of world population
• Common in patients of African descent
• Precipitated by stress, infection, drugs, and
  fava beans
• Hemolysis mostly extravascular but may be
  intravascular if severe case

23
Hemolytic Anemia

• Congenital, continued
• Hemoglobin defects diagnosed by hemoglobin
  electrophoresis
• Thalassemias
• Group of diseases characterized by globin chain
  (alpha and beta) imbalance
• Thalassemia trait most common
• Reduces hgb production within RBCs but overall
  RBC production and survival are normal
• Patients are usually slightly anemic and
  microcytic little to no clinical significance
• Beta thalassemia major / Cooleys anemia
• Mutations impair production of globin chains from
  both beta-globin genes, leaving excess of
  alpha-chains
• Ineffective erythropoiesis
• Transfusion-dependent bone marrow transplant is
  only curative therapy

24
Hemolytic Anemia

• Congenital, continued
• Sickle cell disease
• RBCs become sickle-shaped ? hemolysis, vascular
  occlusion
• Hgb S gene carried by 8 of African Americans
• 1625 have disease
• Genetic counseling available
• Acute crisis may be triggered by dehydration,
  infection, and physiologic stress last hours to
  days
• Bone pain
• Jaundice
• Priapism
• Chest syndrome
• Complications
• Hemosiderosis
• Skin ulcers
• Renal failure
• Avascular necrosis
• Stroke
• Retinopathy
• Severe infections

25
Hemolytic Anemia

• Congenital, continued
• Sickle cell disease
• Crisis Management
• Hydration
• Pain medication
• Exchange transfusion
• Indications include acute chest syndrome, stroke,
  priapism
• Health maintenance
• Folic acid supplementation
• Highly susceptible to infection with encapsulated
  bacteria
• Pneumococcal vaccination!
• Low threshold for antibiotic therapy prophylaxis
  is standard in children
• Hydroxyurea (Hydrea) may reduce crisis frequency
• Best outcomes when patients are followed by
  specialty center (i.e. Grady)
• Life expectancy only 40-50 years

26
Hemolytic Anemia

• Acquired
• Classified according to site of RBC destruction
  and whether mediated by immune system
• Intravascular
• Extravascular
• Autoimmune
• Non-immune
• Many causes be aware of these
• Transfusion of incompatible blood (details
  later)
• Autoimmune
• Warm (IgG-mediated) most common
• Cold (IgM-mediated)
• Prosthetic valves
• TTP/HUS
• DIC
• Cancer
• Drugs

27
Hemolytic Anemia

• Coombs Test (DAT)
• Patient RBCs washed free of plasma and mixed with
  IgG or complement
• Agglutination is a positive result, suggesting
  autoimmune hemolytic process
• Treatment
• Consult hematology
• Folate
• Steroids
• Splenectomy (refractory cases)

28
Polycythemia / Erythrocytosis

• Abnormal elevation of hemoglobin
• Rule out relative polcythemia caused by
  contraction of plasma volume, e.g. dehydration
• Primary
• Polycythemia Vera
• RBC production independent of EPO
• EPO level is low / positive JAK-2 is diagnostic
• Uncommon
• May be associated with leukocytosis,
  thrombocytosis, splenomegaly
• Hyperviscosity
• Headache, vertigo, visual changes, mental
  confusion
• Risk of transformation into acute leukemia
• Refer to hematology
• Secondary
• RBC production in response to increased EPO
  production
• EPO level is usually high
• Very common
• Usual etiology is chronic hypoxia (COPD, sleep
  apnea)
• Phlebotomy (250-500 mL) to maintain hct 45-50
  treat underlying problem!

29
White Blood Cells

• Differential
• Neutrophils 45-65
• Segs / Polys
• Lymphocytes 15-40
• Monocytes 2-8
• Eosinophils 0-5
• Basophils 0-3
• Do you remember the physiologic role of each type
  of WBC?

30
Leukopenia

• Neutropenia is most common cause
• Absolute neutrophil count (ANC) lt 1.5 x 109
  cells/L
• Many causes
• Benign racial neutropenia common
• African Americans and Yemenite Jews may have ANC
  as low as 1.0
• Viral infections
• Epstein-Barr, Hepatitis B, HIV
• Drugs
• Careful review of medications be suspicious of
  any medication recently started in patient with
  acute onset neutropenia
• See next slide
• Splenomegaly
• Autoimmune disorders
• SLE (lupus), Rheumatoid Arthritis, etc.
• Bone marrow disorders

31
Neutropenia
32
Leukocytosis

• WBC count gt 11,000
• Determine which type of WBC is leading to the
  leukocytosis
• Neutrophilia most common
• Infection
• Connective tissue disorders
• Medications (especially steroids, growth factors)
• Cancer (CML and solid tumors)
• Myeloproliferative disorders
• Cigarette smoking
• Stress (physiologic)
• Pain, seizure, trauma
• Idiopathic

33
Leukocytosis

• Patients with acute bacterial infection often
  present with neutrophilia and band formation
  i.e. left shift
• Bands young neutrophils
• Viral infections are usually associated with low
  WBCs leukocytosis may suggest complications
• Ex bacterial pneumonia with underlying influenza
  infection

34
Leukocytosis

• Lymphocytosis
• Viral infections
• HBV, HCV, EBV, CMV
• Tuberculosis
• Pertussis
• Drug Reaction
• Stress (physiologic)
• Trauma, MI, cardiac arrest, sickle crisis
• Malignancy
• ALL, CLL, lymphoma

35
Chronic Leukemia

• Chronic myelogenous leukemia (CML)
• Translocation between long arms of chromosomes 9
  and 22 Philadelphia Chromosome bcr/abl
  protein
• Patients usually middle-age at diagnosis, average
  age 55 years
• Fatigue, fever, night sweats, abdominal fullness
  (splenomegaly)
• Symptoms of leukostasis may be present if WBC gt
  500,000
• Blurred vision, respiratory distress, priapism
• Three phases of disease
• Early / Chronic phase
• Accelerated
• Blast crisis

36
Chronic Leukemia

• CML, continued
• Recognize early CML from infection
• WBC usually lt 50,000 with infection
• WBC average 150,000 at time of diagnosis with CML
• LAP score is decreased
• Splenomegaly NOT present with infection
• Chromosomal abnormality and detection of bcr/abl
  protein by peripheral blood PCR is diagnostic of
  CML
• Treatment
• Refer to hematologist
• Despite very high WBC, not an emergency unless
  leukostasis is suspected
• Imatinib (Gleevec) - released in 2001
• 98 response rate in chronic phase patients
• 80 of patients alive and stable at 7 years
• Allogeneic BMT is only cure
• Reserved for select patients

37
Chronic Leukemia

• Chronic lymphocytic leukemia (CLL)
• Clonal malignancy of B-lymphocytes
• Course is usually indolent affects older
  patients, average age at diagnosis is 70 years
• Often found incidentally
• Fatigue, lymphadenopathy common
• Hepatosplenomegaly
• Immunodeficiency is major clinical concern
• Lymphocytes are defective do not make
  antibodies in response to antigens
• Treatment
• Observation
• Indications for therapy include progressive
  fatigue, symptomatic lymphadenopathy, anemia, or
  thrombocytopenia
• Rituximab (Rituxan) and fludarabine /-
  cyclophosphamide is initial approach
• Gamma globulin (IVIG) used in patients with
  recurrent or severe bacterial infections
• Allogeneic BMT is potentially curative but
  reserved for select patients
• Prognosis improving survival is 10-15 years
  with early disease

38
Acute Leukemia

• Acute Myelogenous Leukemia (AML)
• Most common in adults
• Usually no apparent cause
• Exposure to radiation, benzene, and certain
  chemotherapy drugs (alkylators) associated with
  leukemia
• Underlying myelodysplastic syndrome (MDS) is risk
  factor
• Symptoms and signs
• Related to replacement of marrow space by
  malignant WBCs
• Patients often very ill for period of just days
  or weeks
• Skeletal pain
• Bleeding
• Gingival hyperplasia
• Infection
• Pancytopenia with circulating blasts is hallmark
  bone marrow biopsy required
• Auer rods on peripheral smear are pathognomonic

39
Acute Leukemia

• AML, continued
• Management
• Immediate referral to hematologist
• Patients often hospitalized for therapy
• Anthracycline (daunorubicin or idarubicin) plus
  cytarabine results in CR in 80 of patients lt 60
  years
• Additional high dose chemotherapy following CR
  leads to cure rate of 35-40
• Acute Lymphocytic Leukemia (ALL)
• More often seen in children

40
Lymphoma

• Hodgkins disease
• Malignancy of B-lymphocytes
• Reed-Sternberg cells
• Various subtypes nodular sclerosing is most
  common
• Bimodal age distribution (20s and 50s)
• Painless lymphadenopathy /-B-symptoms
• Fever, night sweats, weight loss (10 over 6
  months)
• Generalized pruritis
• Ann Arbor staging system based on distribution of
  involved lymph nodes
• Treatment is XRT for very low risk patients
  most will require chemotherapy, i.e. ABVD
• Good prognosis many patients are cured

41
Lymphoma

• Non-Hodgkins Lymphoma (NHL)
• Heterogeneous group of cancers affecting
  lymphocytes
• Usually classified by histologic grade (low to
  high)
• Follicular lymphoma
• Small lymphocytic lymphoma
• Diffuse large B-cell lymphoma
• Burkitts lymphoma
• Many others
• Painless lymphadenopathy, often involving
  retroperitoneum, mesentery, or pelvis
• Extranodal disease may be present, i.e. skin and
  GI tract
• Diagnosis by tissue biopsy molecular profiling
  assists in classification
• Staging involves CT imaging and sometimes bone
  marrow biopsy
• LDH is important prognostic marker

42
Lymphoma

• NHL, continued
• Treatment
• Observation in select patients
• Chemotherapy
• Immunotherapy (i.e. monoclonal antibodies)
• Rituximab (Rituxan) anti-CD20
• Radiation
• Prognosis
• Low grade lymphoma is often chronic disease with
  remissions and relapses median survival 6-8
  years
• Patients with higher grade lymphoma are often
  treated with curative intention
• International Prognostic Index (IPI) allows for
  risk stratification

43
Myeloma

• Malignancy of plasma cells
• Abnormal paraproteins are created leading to
  systemic problems
• IgG 60
• IgM 20
• Must be able to recognize in primary care setting
• CRAB calcium, renal, anemia, bone
• Primarily disease of elderly (median age 65
  years)
• Males gt Females
• Most common hematologic malignancy among African
  Americans 2 among Caucasians

44
Myeloma

• Presentation
• Symptoms usually related to bone pain, anemia, or
  recurrent infections
• Pathologic fractures
• Signs
• Pallor
• Bone tenderness
• Plasmacytoma
• Lab findings
• Anemia
• Rouleau formation on peripheral smear
• Hypercalcemia
• Total protein elevated with high globulin
  fraction and low albumin
• ESR, CRP, ALK, B2M often elevated
• Paraprotein (monoclonal gammopathy) detected by
  serum protein electrophoresis (SPEP)
• 15 of cases are non-secretory
• Light chains pass through glomerulus and detected
  in urine (UPEP)

45
Myeloma

• Presentation, continued
• Skeletal survey shows osteolytic lesions
• Do not confuse with bone scan used for solid
  tumors
• Bone marrow biopsy required
• Shows infiltration of plasma cells into marrow
  space ranging from 20-100
• Chromosomal abnormalities are common
• Diagnosis is made based on specific criteria
• MGUS is diagnosis of exclusion
• Durie-Salmon staging system used to guide initial
  therapy
• Observation
• Chemotherapy
• BMT
• Hospitalization indicated for acute renal
  failure, hypercalcemia, or suspicion of spinal
  cord compression
• Disease is not curable although long remissions
  are possible prognosis is improving
• Average survival 6 years

46
Myeloma

• Osteolytic lesions

47
Bleeding Disorders

• Coagulation cascade

48
Bleeding Disorders

• Review coagulation cascade general
  understanding is essential for clinical practice
• Prothrombin time (PT) evaluates extrinsic system
• Factors I, II, V, X, VII
• Activated partial thromboplastin time (PTT)
  evaluates intrinsic system
• Factors I, II, V, X, VIII, IX, XI, XII
• Bleeding time reflects platelet number and
  function

49
Bleeding Disorders

• General approach
• Prolonged PT only
• Warfarin (Coumadin) therapy
• Factor VII deficiency
• Fibrinogen abnormality
• Prolonged PTT only
• Heparin therapy
• Factor VIII deficiency
• Congenital
• Hemophilia A (X-linked)
• 15000 male births
• Male and female carriers no racial predilection
• Acquired
• Factor IX deficiency Hemophilia B / Christmas
  disease
• Lupus anticoagulant
• Antiphospholipid antibodies
• Prolonged PT and PTT
• Usually reflective of general medical condition
  such as DIC, vitamin K deficiency, or liver
  disease
• Disorders of common pathway (rare)

50
Bleeding Disorders

• Approach to patient
• History of trauma? Time between injury and
  bleeding?
• Ask about bleeding at times of life events
• Circumcision
• Tooth eruption
• Dental extraction
• Ear piercing
• Childbirth
• Menstrual cycles
• Family history
• 30 of patients with hemophilia have unremarkable
  FH because of de novo mutation of X chromosome

51
Bleeding Disorders

• Patterns of bleeding
• Primary hemostasis platelet and vascular
  function
• Secondary hemostasis clotting factors

52
Bleeding Disorders

• Treatment
• Hemophilia patients are best managed by specialty
  center
• Recombinant factor concentrates used
  prophylactically in young children
• Adults treated as needed for bleeding episodes or
  prior to high risk activities
• Patients with mild disease may respond to DDAVP

Acute hemarthrosis
53
Bleeding Disorders

• von Willebrand Disease
• Most common inherited bleeding disorder
• 1 of population affected
• Deficiency of von Willebrand factor
• vWF is a protein that binds platelets together
  and allows for adhesion at site of vascular
  injury
• vWF also binds to Factor VIII to prolong its
  half-life in circulation
• Bleeding is usually mild to moderate and involves
  skin and mucous membranes
• DDAVP is primary treatment releases vWF and
  factor VIII from storage sites

54
Bleeding Disorders

• Immune Thrombocytopenia (ITP)
• Autoimmune condition antibodies bind platelets
  leading to destruction
• Often found incidentally mild mucosal bleeding,
  petechial rash may be present
• Diagnosis of exclusion must rule out medication
  effect, HIV, and HBV/HCV infection
• Antiplatelet antibody screening NOT recommended
  due to low sensitivity and specificity
• Bone marrow biopsy NOT required except in elderly
  or refractory cases
• Treatment
• Stop unnecessary medications
• Steroids (Prednisone 1 mg/kg/day x 7-10 days,
  then taper)
• Intravenous immune globulin (IVIG)
• Anti-D (WinRho)
• Splenectomy
• Platelet transfusion used for emergency only as
  may actually exacerbate condition

55
Bleeding Disorders

• Petechiae in patient with acute ITP platelet
  count 10,000

56
Thrombosis

• Venous thromboembolism (VTE)
• DVT and PE are very common in hospital setting
• 20 among general medical patients up to 80 of
  critical care patients
• Be familiar with risk factors
• Obesity
• Oral contraceptives
• Pregnancy
• Tobacco abuse
• Prolonged immobility
• Surgery
• Malignancy
• Consider prophylaxis
• Compression stockings and sequential compression
  devices
• Lovenox 40 mg SQ once daily
• Arixtra 2.5 mg SQ once daily
• Unfractionated heparin 5000 units q 8-12 hours

57
Thrombosis

• Treatment of VTE
• Parenteral followed by oral (long-term)
  anticoagulation
• LMWH (Lovenox) preferred over UFH for its stable
  pharmacokinetics, ease of dosing, and lower risk
  of allergy
• 1 mg per kg SQ q12h
• Contraindicated in patients with CrCl lt 30
• Consider UFH (short half-life) in patients with
  epidurals or those who are being considered for
  thrombolysis
• Bolus omitted when risk for bleeding is thought
  to be elevated
• Protamine heparin antidote
• Arixtra
• Factor Xa inhibitor
• Easy dosing
• 7.5 mg SQ q24h for patients 50-100 kg weight
• 10 mg SQ q 24h for patients gt 100 kg
• No increased risk in bleeding over LMWH although
  slightly longer half life

58
Thrombosis

• Treatment of VTE, continued
• Warfarin (Coumadin)
• Oral vitamin K antagonist
• Dietary teaching required
• MANY interactions
• Required for minimum of 3 months to reduce risk
  of recurrent thrombosis
• Starting dose usually 5 mg qd but requirements
  lower in elderly, Asian descent, hyperthyroidism,
  CHF, liver disease, malnutrition
• Vitamin K (Mephyton) is antidote for warfarin
  toxicity
• Give 2.5 to 5 mg for INR gt/ 9
• Consider for INR 5-9 in patients at high risk for
  bleeding
• Oral route preferred SQ absorption is erratic
  and not recommended
• Intravenous infusion must be slow (i.e. over 30
  min) and closely monitored given risk for
  anaphylaxis

59
Thrombosis

• Heparin-Induced Thrombocytopenia (HIT)
• Occurs in 3 of patients exposed to UFH 0.6
  with LMWH
• Drop in platelet count 50 within 5-10 days of
  heparin exposure
• May occur within 48 hours of exposure in those
  previously exposed to drugs
• Thrombosis (NOT bleeding) is of great clinical
  concern
• Thrombotic events detected in about half of HIT
  patients
• Must STOP heparin and consult hematology
• Direct thrombin inhibitor (alternative
  anticoagulant) may be started
• Argatroban
• Refludan

60
Transfusion Medicine

• History
• 19th century experimentation with animal and
  human blood transfusion
• 1900 ABO blood groups first described
• 1936 First US hospital blood bank established
• Blood donation
• Approximately 450 mL whole blood collected
  later processed into RBC, plasma, and platelets
• Apheresis removing whole blood, separating a
  portion, and returning the rest to donor
• Used for plasma and platelet donation
• RBC storage period ranges 35-42 days depending on
  preservative
• Up to 25 of transfused RBCs will be cleared from
  recipient circulation within 24 hours of delivery
  

61
Transfusion Medicine

• Review of physiology
• Anti-A and Anti-B are naturally occurring and
  develop in first months of life in those lacking
  A or B antigens on RBC surface
• Rh factor (D-antigen) absent in 15 of population
• These patients may develop anti-D antibodies
  following pregnancy or transfusion with Rh blood
  leading to severe reactions
• Pretransfusion testing
• ABO and Rh typing
• Antibody screen (Coombs test)
• If positive, further testing required to identify
  specific antibody donor unit is then checked
• Crossmatch
• Donor RBC mixed with recipient serum and
  incubated to check for compatibility
• Type O negative blood may be used in emergency
• Limited supply only 15 of donors

62
Transfusion Medicine

• When to transfuse blood? Use clinical judgment!
• No single hgb/hct limit general indications
  include
• Symptomatic anemia
• Tachypnea, Tachycardia, Cyanosis
• Blood loss (gt15 volume)
• Chronic hypoproliferative anemia (i.e. MDS)
• Sickle cell crisis
• Single unit of PRBC increases hgb by 1.5 g/dL or
  hct by 3-4

63
Transfusion Medicine

• Platelet transfusion
• Platelet count lt 10,000
• Active bleeding in setting of significant
  thrombocytopenia
• Platelet count of 50,000 adequate for most
  surgical procedures
• Single apheresis unit will generally raise
  platelet count by 30,000
• Anticipate low yield with splenomegaly, DIC,
  sepsis
• Immune factors may also cause patients to be
  refractory
• Consider ordering HLA-matched platelets
• Relative contraindications
• ITP, TTP, and HIT

64
Transfusion Medicine

• Plasma transfusion
• Indications
• Coagulation factor deficiency
• Consider factor concentrates if available
• Rapid reversal of warfarin effect
• Hemorrhage in patients with liver disease
• DIC (controversial)

65
Transfusion Medicine

• Transfusion Reactions
• Acute hemolytic reaction
• Intravascular hemolysis (hemoglobinuria)
• Fever, chills, pain, nausea, dyspnea, hypotension
• May lead to ARF, DIC, and death
• ABO incompatibility (human error) is most common
  cause
• Proper labeling and patient identification is
  essential for prevention
• STOP transfusion and notify blood bank
  immediately
• Delayed hemolytic reaction
• Occur days to weeks later
• Caused by RBC antibodies not detected by
  pretransfusion testing
• Febrile non-hemolytic reaction
• Common in patients with multiple prior
  transfusions
• Caused by cytokines or recipient antibodies to
  donor leukocytes
• Allergic reaction
• Associated with plasma may be related to
  residual plasma in PRBC specimen
• Usually mild pruritis, flushing, urticaria
• Occasional anaphylaxis

66
Transfusion Medicine

• Transfusion reactions, continued
• Hypotensive reaction
• Caused by bradykinin generation
• Patients on ACE inhibitors at higher risk
• Hypotension and tachycardia shortly after
  beginning transfusion BP returns to baseline
  upon interruption
• Usually safe to resume at slower rate upon
  recovery
• Bacterial contamination
• Septic shock high mortality
• Rare but unpredictable
• Transfusion-related acute lung injury (TRALI)
• Occurs during or shortly after transfusion
• Causes leakage of pulmonary capillaries
  presenting as pulmonary edema in absence of heart
  disease
• Resolves within 48-72 hours
• Mortality rate is 10

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Transfusion Medicine

• Risks of infectious disease
• Hepatitis B
• Risk 1200,000 per unit
• Hepatitis C
• Greatest risk
• Approximately 25 of HCV-infected patients
  worldwide report history of prior blood
  transfusion
• Cytomegalovirus (CMV)
• Very serious in immunocompromised patients
• Specify CMV negative donor in these populations!
• HIV
• Incidence of transfusion-associated disease
  peaked in 1985 now very rare
• Deferral of high risk donors and modern testing
  methods have reduced risk to approximately
  12,000,000 per unit

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Case Study 1

• A 60-year-old male presents with fatigue. PMH is
  significant for Crohns disease. On examination,
  his tongue is fissured and decreased vibratory
  sensation is noted in the lower extremities. You
  order a CBC and review the results
• WBC 8,100
• Hgb 10.1 g/dL
• Hct 31
• MCV 124
• Plts 160,000
• What is your preliminary diagnosis? What test(s)
  would be helpful to further evaluate this
  patient?

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Case Study 2

• A 48-year-old African American man presents to
  the ED with acute onset of dyspnea while mowing
  the grass. PMH is unremarkable. A CBC shows the
  following
• WBC 6,100
• Hgb 5.8 g/dL
• Hct 20.1
• MCV 65
• Plts 254,000
• Which diagnosis is the most likely cause of his
  symptoms?
• A) Sickle cell anemia with crisis
• B) Thalassemia
• C) Iron deficiency
• D) Hemolytic anemia
• E) TTP

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Case Study 3

• An overweight 20-year-old female presents to your
  clinic with fatigue and menometrorrhagia. She is
  accompanied by her mother who states she is
  chewing ice all the time. You suspect iron
  deficiency and order an iron panel.
• How do you expect each parameter to result low
  or high?
• Serum iron
• Total iron binding capacity (TIBC)
• Iron saturation
• Ferritin

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Case Study 4

• A 25-year-old African American is admitted to
  your service with sickle cell crisis. He
  presented with abdominal and bilateral leg pain,
  similar to past episodes. You receive a call
  that he is now experiencing chest pain, worse
  with inspiration.
• Vitals T 101F BP 110/78 P 100 R 25 O2
  sat 92 on 2L per min by NC
• Examination reveals scleral icterus and
  tenderness with tibial palpation
• Labs reveal WBC 15,000 Hgb 8.2 g/dL Retic 10
  Total bilirubin 6
• What is the most likely problem?
• What is your next step?
• What are the complications?

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Case Study 4
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Case Study 4

• This patient has acute chest syndrome which is
  associated with sickling in lung tissue and/or
  pneumonia. A chest x-ray should be obtained and
  empiric antibiotics initiated.
• It is virtually impossible to distinguish whether
  or not infection is present. Progressive
  pulmonary infiltrates may be seen on CXR.
  Complications include respiratory failure and
  death.

74
Case Study 5

• A 52-year-old Hispanic truck driver presents for
  routine physical examination. He has not been to
  the doctor in years but comes at the
  persistence of his wife. PMH unremarkable. He
  takes no medications. ROS significant for
  fatigue and weight loss. You order routine labs
  as well as a CXR which is normal.
• CBC shows WBC 1,100 (ANC 0.6) Hgb 14
  platelets 110,000
• CMP unremarkable except total protein and albumin
  are decreased
• What is your differential diagnosis? How would
  you proceed?

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References

• Desai, SP. Clinicians Guide to Laboratory
  Medicine. Cleveland Lexi-Comp, 2004.
• McPhee SJ, Papadakis MA. Current Medical
  Diagnosis and Treatment. New York McGraw Hill,
  2010.
• Schmaier AH, Petruzzelli LM. Hematology for the
  Medical Student. Philadelphia Lippincott,
  Williams, and Wilkins, 2003.