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193 Cards in this Set

  • Front
  • Back
Compensatory mechanisms associated with anemia
1) Increased CO
2) Increased extraction ratio
3) Rightward shift of oxyhemoglobin curve (Increased 2,3-DPG)
4) Expansion of plasma volume
Indications for blood transfusion
1) Hb concentration less than 7g/dL
2) Pt requires increased oxygen-carrying capacity
Clinical features of anemia
1) Pallor (conjunctiva)
2) HYPOtension & Tachycardia
3) Nonspecific complaints - HA, fatigue, poor concentration, diarrhea, nausea
4) Signs of underlying cause - jaundice (hemolytic anemia), melena (GI bleed)
Changes in H/H expected after 1 unit of PRBC transfusion
Hb increases by 1 point
Hct increases by 3 points
Decrease in H/H secondary to dilution of blood (i.e., volume infusion)
Tested to determine whether or not erythropoeisis is occurring in the bone marrow
Reticulocyte index

*Index > 2% --> excessive RBC destruction or loss
*Index < 2% --> inadequate RBC production
Fresh Frozen Plasma (FFP)
Contains all clotting factors
Given for high PT/PTT, coagulopathy, and deficiency of clotting factors
Contains factor VIII and fibrinogen
Given for hemophilia A, decreased fibrinogen (DIC) and vWD

*Also has vWF and Factor XIII
Expected increase with platelet transfusion
1 unit raises count by 10,000
Cause of intravascular hemolysis
ABO-mismatched blood transfusion

*Symptoms: Fever/chills, n/v, flank/back pain, dyspnea
Differential diagnosis of microcytic anemia
1) Iron-deficient anemia
2) Thalessemia
3) Anemia of chronic disease
4) Ringed sideroblastic anemia
Differential diagnosis of macrocytic anemia
1) Vitamin B12 deficiency
2) Folate deficiency
3) Liver disease (altered shape of RBCs due to altered metabolism of plasma lipoproteins)
4) Stimulated erythropoiesis (reticulocytes larger than mature RBCs)
Differential diagnosis of normocytic anemia
1) Aplastic anemia
2) Anemia of chronic disease (chronic inflammation, malignancy)
3) Tumor
4) BM fibrosis
5) Renal failure (decreased erythropoietin)
MCC of anemia worldwide
Iron-deficiency anemia

*Chronic blood loss (menstruation or GI bleeding)
*Dietary deficiency/increased iron requirements (infancy, adolescence, pregnancy)
Most reliable test for iron deficiency anemia
Serum ferritin (will be decreased)

*BM biopsy (gold standard) and Guaiac stool test also done
Labs in iron deficiency anemia
1) Decreased serum ferritin
2) Increased TIBC
3) Elevated transferrin
4) Decreased serum iron
5) Microcytic, hypochromic RBCs
Treatment of iron deficiency anemia
1) Oral iron replacement (ferrous sulfate)
2) Parenteral iron replacement (IV or IM)
3) Blood transfusion not recommended unless anemia is severe or pt has cardiopulmonary dz
SEs of Ferrous Sulfate
2) Nausea
3) Dyspepsia
Inherited disorders characterized by inadequate production of either alpha or beta globin chains of hemoglobin
Cooley's anemia
Homozygous beta-chain thalassemia

*Mediterranean populations
Clinical features of Cooley's anemia
1) Severe anemia (microcytic hypochromic)
2) Massive hepatosplenomegaly
3) Expansion of BM space --> DEFORMITY OF BONES
4) Growth retardation/failure to thrive
5) Death from CHF (if untreated)
Diagnosis of Cooley's anemia
1) Hb electrophoresis --> HbF elevated
2) Peripheral blood smear --> microcytic hypochromic anemia
Treatment of homozygous beta-chain thalassemia
Frequent PRBC transfusions
Treatment for heterozygous beta-chain thalassemia
No treatment necessary

*Pts usually asymptomatic
What must be ruled out in elderly pts with iron deficiency anemia?
Colon cancer
RDW is abnormal in which type of anemia?
Iron deficiency anemia
Given to prevent iron overload in pts with transfusion-dependent thalassemia

*These pts can develop CHF
Alpha thalassemia common in AAs
Alpha thalassemia minor (mutation/deletion of 2 alpha loci)

*mild microcytic hypochromic anemia --> no treatment necessary
HbH disease
Mutation/deletion of 3 alpha loci
1) Hemolytic anemia
2) Splenomegaly
3) Electrophoresis shows HbH
Mutation/deletion of all 4 alpha loci
Hemoglobin Barts - usually fatal at birth (Hydrops Fetalis) or shortly after birth
Sideroblastic anemia
Abnormality in RBC iron metabolism

*Can be caused by drugs, lead exposure, collagen vascular disease, and neoplasms
Laboratory findings of sideroblastic anemia
1) Increased serum iron
2) Increased ferritin
3) Normal TIBC
4) Ringed sideroblasts in BM

*PYRIDOXINE for treatment
Basis of Anemia of Chronic Disease
The release of inflammatory cytokines has suppressive effect on erythropoiesis

*No treatment necessary
Aplastic anemia
BM failure leading to pancytopenia

*BM biopsy for definitive diagnosis
Causes of aplastic anemia
1) Idiopathic
2) Radiation exposure
3) Medications
4) Viral infections
5) Chemicals
Medications associated with aplastic anemia
1) Chloramphenicol
2) Sulfonamides
3) Gold
4) Carbamazepine
Clinical features of aplastic anemia
1) Anemia - fatigue, dyspnea
2) Thrombocytopenia - petechiae, easy bruising
3) Neutropenia - increased incidence of infections
4) Can become acute leukemia
Reactions requiring vitamin B12
1) Conversion of homocysteine to methionine
2) Conversion of methylmalonyl CoA to succinyl CoA (catabolism of branched-chain amino acids and odd-chain fatty acids)
Vitamin B12 stores in the liver
Plentiful; can sustain a person for 3 years

*Dietary sources: meat & fish
*Absorbed in terminal ileum attached to intrinsic factor
Causes of vitamin B12 deficiency
1) Pernicious anemia - deficiency of intrinsic factor
2) Gastrectomy
3) Poor diet or alcoholism
4) Crohn's disease, ileal resection
5) Organisms competing for B12 (tapeworm, bacteria)
Clinical features of vitamin B12 deficiency
1) Megaloblastic anemia
2) SORE TONGUE (stomatitis & glossitis)
3) Neuropathy
Describe the neuropathy seen in B12 deficiency
Demyelination of posterior columns, lateral corticospinal tracts, and spinocerebellar tracts --> LOSS OF POSITION/VIBRATORY SENSE, ATAXIA, UPN signs

Peripheral blood smear in B12 deficiency
1) Megaloblastic anemia (MCV > 100)
2) Hypersegmented neutrophils
Elevated precursors in B12 deficiency
1) Methylmalonic acid
2) Homocysteine
Pathology of Pernicious Anemia

*Inadequate production of intrinsic factor
Schilling test
Determines the cause of B12 deficiency
1) Give IM dose of unlabeled B12 to saturate binding sites
2) Give radioactive B12; measure urine & plasma levels to determine absorption
3) Repeat radioactive B12 with addition of intrinsic factor

*Malabsorption --> no improvement in serum levels
*Pernicious anemia --> improved absorption, increased serum levels
Treatment of B12 deficiency
Parenteral B12 therapy q monthly (Cyanocobalamin)
Main source of folate
Green vegetables

*Inadequate intake over 3 months can cause deficiency
Causes of folate deficiency
1) Pregnancy
2) Seizure medications (phenytoin)
3) Inadequate dietary intake / alcoholism
4) Long-term oral antibiotics
5) Increased demand
6) Hemolysis
7) Folate antagonists (MTX)
8) Hemodialysis
Location of a murmur refers to?
where the heart murmur is auscultated best on the anterior chest to listen for heart murmurs
Hemolytic anemia
Premature destruction of RBCs
Congenital or acquired
Low Haptoglobin levels
Elevated LDH
Elevated indirect bilirubin

*HAPTOGLOBIN binds to Hb, so it is low when Hb is destroyed
Sickle Cell Anemia (HbS)
Autosomal recessive --> Valine replaced by glutamic acid at 6th position of beta chain
Hb polymerizes under low oxygen conditions --> Sickled RBCs obstruct small vessels --> Ischemia
Prognosis of HbS
Life expectancy reduced by 25-30 yrs
Survival depends on frequency of vaso-occulsive crises
Clinical features of HbS
1) Severe, lifelong hemolytic anemia
2) Jaundice, pallor
3) Gallstones (pigmented)
4) High-output CHF (due to anemia)
5) Aplastic crisis (Parvovirus B19)
Treatment of Aplastic Crisis
Blood transfusion
Findings associated with vaso-occlusion in HbS
1) Painful crisis in bone
2) Hand-foot syndrome (dactylitis)
3) Acute chest syndrome (similar to pneumonia)
4) Splenic infarction (autosplenectomy)
5) Avascular necrosis of joints
6) Priaprism
7) CVAs
8) Ophthalmologic complications
9) Renal papillary necrosis
10) Infections - encapsulated bacteria, Salmonella osteomyelitis
Role of Hydroxyurea in HbS
Enhances HbF levels
Accelerates healing of leg ulcers and reduces recurrence
Hereditary Spherocytosis
Defect in Spectrin
Loss in RBC membrane surface area -->
Spherical shaped RBCs destroyed in spleen (extravascular hemolysis)
Clinical features of hereditary spherocytosis
1) Hemolytic anemia
2) Jaundice
3) Splenomegaly
4) Gallstones (pigment stones)
5) Hemolytic crises
Diagnosis of hereditary spherocytosis
1) Osmotic fragility test (hypotonic saline)
2) Elevated reticulocyte count
3) Sphere-shaped RBCs (spherocytes)
4) Negative Direct Coombs test
Treatment of hereditary spherocytosis
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
1) X-linked recessive (mostly men)
2) Precipitated by sulfas, fava beans, malaria drugs, infection

*Mild form - African Americans --> only old RBCs affected
*Severe form - Mediterranean people --> old and new RBCs affected
Heinz bodies
Denatured Hb, resulting from unneutralized H2O2 in RBCs

*Seen in G6PD deficiency
Bite cells
RBCs after the removal of Heinz bodies by splenic macrophages

*Seen in peripheral smear of G6PD
Diagnosis of G6PD deficiency
1) Peripheral blood smear: Heinz bodies & Bite cells
2) Deficient NADPH formation
3) Measurement of G6PD
Treatment of G6PD deficiency
1) Avoid drugs that cause hemolysis
2) Maintain hydration
3) RBC transfusion when necessary
Autoimmune Hemolytic Anemia (AIHA)
Production of autoantibodies against RBC membrane antigens --> leads to destruction of RBCs

*Antibodies bind at particular temperatures
1) IgG antibody binds at 37 degrees Celsius
3) Idiopathic, or 2/2 to malignancies or collagen vascular diseases or drugs

*More common than cold AIHA
1) IgM antibody binds at 4 degrees Celsius
2) COMPLEMENT ACTIVATION and intravascular hemolysis --> Liver sequestration
3) Idiopathic or 2/2 infection (MYCOPLASMA PNEUMONIAE)
Clinical features of AIHA
1) Si/Sx of anemia
2) Jaundice
3) Features of underlying disease
Diagnosis of AIHA
1) Direct Coombs test
2) Cold agglutinin titer
Treatment of AIHA
Warm AIHA: glucocorticoids (Prednisone), splenectomy, immunosuppression, RBC transfusion, folic acid supplements

Cold AIHA: avoid cold, RBC transfusion, chemotherapy *steroids NOT helpful

*Usually no treatment necessary for AIHA
Paroxysmal Nocturnal Hemoglobinura (PNH)

*Also known as Marchiafava-Micheli syndrome
Acquired deficiency of anchor proteins that link complement-inactivated proteins to blood cell membranes --> increased susceptibility of RBCs, WBCs, and platelets to complement-mediated lysis
Clinical features of PNH
1) Chronic intravascular hemolysis
2) Normochromic normocytic anemia
3) Pancytopenia
4) Venous thrombosis (Budd-Chiari)
5) Musculoskeletal pain
Diagnosis of PNH
1) Ham's test
2) Sugar water test
3) Flow cytometry for CD55 and CD59

*CD55 and CD59 are anchoring proteins that also protect WBCs and RBCs from destruction by complement; when absent due to mutation, cells are attacked
Ham's test
Patient's cells incubated with acidified serum --> alternative complement pathway leads to lysis of PNH cells but not normal cells
Treatment of PNH
1) Glucocorticoids (most pts don't respond)
2) Bone marrow transplant
Platelet count less than 150,000

Normal is 150,000 - 450,000

*Can occur in splenomegaly via sequestration
Causes of thrombocytopenia - decreased production
1) Bone marrow failure (aplastic anemia, FANCONI SYNDROME)
2) Bone marrow invasion (tumors, fibrosis)
3) Bone marrow injury (drugs, chemicals, radiation, infection)
Causes of thrombocytopenia - increased destruction
1) Immune (infection, drug-induced, ITP, SLE, HIT-2, HIV)
2) Nonimmune (DIC, TTP, HIT-1)
Diagnosis of thrombocytopenia
1) CBC
2) Bleeding time, PT, PTT
Heparin-induced thrombocytopenia
HIT-1: Heparin directly causes platelet aggregation >48 hrs
HIT-2: Heparin induces antibody-mediated injury to platelet 3-12 days after administration
Clinical features of thrombocytopenia
1) Cutaneous bleeding (petechiae, ecchymoses
2) Mucosal bleeding (epistaxis, menorrhagia, hemoptysis, GI bleeds)
3) Excessive bleeding after surgery
4) Intracranial hemorrhage and heavy GI bleeds

*NO hemarthroses or hematomas
Treatment of thrombocytopenia
1) Treat underlying cause
2) Platelet transfusion
3) Discontinue NSAIDS, antiplatelets, and anticoagulants
Immune Thrombocytopenic Purpura (ITP)
Autoimmune antibody (IgG) formation against platelets --> damaged platelets are removed by splenic macrophages
Acute ITP
Seen in children after viral infection
Self-limited - 80% resolves in 6 months
Chronic ITP
Usually seen in women 20-40 yrs old
Spontaneous remission rare
Clinical features of ITP
1) Petechiae and ecchymoses of skin
2) Bleeding of mucous membranes
3) *NO Splenomegaly
Diagnosis of ITP
1) Platelet count : usually <20,000
2) Peripheral smear
3) Bone marrow aspiration - increased megakaryocytes
4) Increased platelet-associated IgG
Treatment of ITP
1) Adrenal corticosteroids
2) IV immune globulin (saturates RES system)
3) Splenectomy
4) Platelet transfusions
Thrombotic Thrombocytopenic Purpura (TTP)
Disorder of unknown platelet consumption
Microthrombi occlude small vessels and cause mechanical damage to RBCs
Clinical features of TTP
1) Hemolytic anemia
2) Thrombocytopenia
4) Fever
5) Neurologic signs (AMS to hemiplegia)
Treatment of TTP
1) Plasmaphoresis
2) Corticosteroids and splenectomy

**Platelet transfusion contraindicated
Bernard-Soulier Syndrome
Autosomal recessive disorder of PLATELET ADHESION TO ENDOTHELIUM
Deficiency of GPIb-IX
Platelets abnormally large
Platelet count mildly low

*GPIb is the receptor for von Willebrand factor
Glanzmann's Thromboasthenia
Autosomal recessive
Disorder of PLATELET AGGREGATION - deficiency of GPIIb-IIIa
*Prolonged bleeding time, normal platelet count

*GPIIb-IIIa has the ability to bind fibrinogen
von Willebrand's Disease (vWD)
Autosomal dominant deficiency or defect in vWF

*MC inherited bleeding disorder
*vWF carries factor III in the blood and enhances platelet aggregation and adhesion
3 subtypes of vWD
Type 1 - decreased levels of vWF (MC)
Type 2 - qualitative abnormalities of vWF
Type 3 - absent vWF (LC)
Clinical features of vWD
1) Cutaneous and mucosal bleeds
2) Menorrhagia
3) GI bleeding possible
Diagnosis of vWD
Clinical & laboratory findings:
Prolonged bleeding time, decreased vWF, decrease factor VIII activity, reduced ristocetin-induced platelet aggregation
Treatment of vWD
1) DDAVP (desmopressin)
2) Factor VIII concentrations (especially type 3 vWD)
*Avoid cryoprecipitate, aspirin/NSAIDs
DDAVP (desmopressin)
Synthetic analog of Vasopressin
Used to treat vWD types 1 & 2 and hemophilia A
Induces endothelial release of vWF (with subsequent increase in Factor VIII) by binding to V1 receptors

*Increases water reabsorption in collecting ducts when bound to V2 receptors*
Hemophilia A
X-linked recessive (males) deficiency of factor VIII
Clinical features of Hemophilia A
1) Hemarthrosis
2) Intracranial bleeding
3) Intramuscular hematomas
4) Retroperitoneal hematomas
5) Hematuria or hemospermia
MC site of hemarthrosis in hemophilila A
Diagnosis of hemophilia A
1) Prolonged PTT
2) Low factor VIII level and normal vWF levels
Treatment of acute hemarthrosis
1) Analgesia - avoid aspirin/NSAIDs
2) Immobilization of joint, ice packs, rest
Treatment of hemophilia A
1) Factor VIII concentrate
2) Desmopressin (DDAVP) - mild disease
Hemophilia B
X-linked recessive
Deficiency of factor IX
Presents similar to hemophilia A
Treatment of hemophilia B
Factor IX concentrate

*DDAVP plays no role
Disseminated Intravascular Coagulation (DIC)
Abnormal activation of coagulation --> Formation of microthombi --> Fibrolysis --> Hemorrhage

*most common in critically ill patients
Causes of DIC
1) Infection - gram-negative sepsis is MCC
2) Obstetric complications
3) Major tissue injury - trauma, burns
4) Malignancy
5) Shock, circulatory collapse
6) Rattlesnake venom
Clinical features of DIC
Bleeding & thrombosis

*End organ infarction, especially in CNS and kidney
Increased in DIC
1) PT, PTT, bleeding time, thrombin time
2) Fibrin split products
3) D-dimer
Decreased in DIC
1) Fibrinogen level
2) Platelet count (thrombocytopenia)
Supportive measures used in treatment of DIC
1) FFP to replace clotting factors
2) Platelet transfusion
3) Cryoprecipitate (fibrinogen and clotting factors)
4) Low does of heparin (thrombosis-dominated picture)
5) Oxygen and IV fluids
Complications of DIC
Intracranial bleeding, stroke, pulmonary embolism, bowel infarction, ARF, arterial occlusion
Vitamin K-associated clotting factors
2,7,9,10, proteins C&S

*post-translational gamma-carboxylation
Causes of vitamin K deficiency
1) Broad-spectrum antibiotics in combination with NPO status
2) TPN (unless it's added)
3) Malabsorption of fat-soluble vitamins
4) Warfarin - vitamin K antagonist
Clotting factor with the shortest t1/2
Factor VII
Clinical features of vitamin K deficiency
1) Hemorrhage
2) PT prolongation; PTT follows
Treatment of vitamin K deficiency
1) Vitamin K replacement - takes several days
2) FFP if bleeding is severe
Why does coagulopathy develop in liver disease?
1) Decreased production of clotting factors
2) Cholestasis causes decreased vitamin K absorption (fat-soluble vitamins ADEK need bile)
3) Hypersplenism (splenomegaly due to portal HTN) causes thrombocytopenia
Clinical features of coagulopathy of liver disease
1) Abnormal bleeding - GI bleeding MC
2) Prolonged PT and PTT
Treatment of coagulopathy of liver disease
1) FFP
2) Vitamin K (cholestasis)
3) Platelet transfusion
4) Cryoprecipitate (fibrinogen deficiency)
Inherited Hypercoagulable States
1) Antithrombin (AT) III deficiency
2) Antiphospholipid Antibody Syndrome
3) Protein C deficiency
4) Protein S deficiency
5) Factor V Leiden (activated protein C resistence)
6) Prothrombin gene mutation
7) Hyperhomocysteinemia
Anti-thrombin (AT) III deficiency
Autosomal dominant

*AT III inhibits thrombin, so deficiency leads to increased clotting
Features of Antiphospholipid antibody syndrome
1) Hypercoagulability
2) Venous or arterial thrombosis
Inhibited by Protein C
1) Factor V
2) Factor VIII

*Deficiency causes unregulated fibrin synthesis
Protein S
Cofactor of Protein C

*Deficiency causes decreased protein C activity
Factor V Leiden
Mutation in factor V gene
*Protein C can no longer inactivate factor V --> unregulated prothrombin activation --> increase in clotting
Clinical features of hypercoagulablity
1) Venous thromboembolism :DVT & PE
Used for permanent anticoagulation with hypercoagulability
Mechanism of action of Heparin
Potentiates the action of antithrombin III to inhibit clotting factors IIa and Xa
Prolongs PTT (intrinsic pathway)

*t1/2 is 1 hour
Indications for heparin use
2) Acute coronary symptoms
3) DVT prophylaxis (Low-dose)
4) Atrial fibrillation
5) After vascular bypass graft
Adverse effects of heparin
1) Bleeding
2) Heparin-induced thrombocytopenia (HIT)
3) Possible osteoporosis
4) Transient alopecia
5) Rebound hypercoagulability after removal (depression of AT III)
Contraindications to heparin
1) Previous HIT
2) Active bleeding
3) Hemophilia, thrombocytopenia
4) Severe HTN
5) Recent surgery on eyes, spine, or brain
Given to reverse the effects of heparin
Protamine sulfate

*FFP given in emergency situation
Mechanism of action of low-molecular-weight heparin (LMWH)
Inhibits factor Xa
Less inhibition of factor IIa and platelet aggregation than heparin

*Does not affect PT or PTT
Administration of LMWH
Subcutaneous injection

*No IV administration
Mechanism of action of Warfarin
Vitamin K antagonist --> Decreases factors 2,7,9,10, protein C, protein S
Prolongation of PT

*Takes 4-5 days for anticoagulation to begin
Adverse effects of warfarin
1) Hemorrhage
2) Skin necrosis
3) Teratogenic - avoid during pregnancy
4) Intracranial bleed
Given to reverse the effects of warfarin
Vitamin K

*Corrects abnormal PT within 4-10 hours with normal liver function
Multiple Myeloma
Neoplastic proliferation of single plasma cell line
Produces monoclonal immunoglobulin
Anemia, leucopenia, thrombocytopenia present in advanced disease
Clinical features of Multiple Myeloma
1) Skeletal manifestations (osteolytic lesions)
2) Anemia (normocytic, normochromic)
3) Renal failure
4) Recurrent infections - MCC of death (2/2 to deprivation of normal immunoglobulins)
5) Amyloidosis
Diagnosis of Multiple Myeloma
1) Serum and urine protein electrophoresis (monoclonal Ig spike - M protein)
2) X-rays (lytic lesions)
3) Bone marrow biopsy (10% abnormal plasma cells)
4) Other findings (hypercalcemia, increased serum protein [hyperglobinemia], rouleaux RBCs, elevated ESR, Bence Jones protein in urine)
Indications for treatment of Multiple Myeloma
1) Hypercalcemia
2) Bone pain
3) Spinal cord compression
Treatment of Multiple Myeloma
1) Systemic chemotherapy (alkylating agents)
2) Radiation
3) Autologous peripheral blood stem cell transplantation
Osteolytic lesions in Multiple Myeloma
Secondary to activation of osteoclast-activating factor by neoplastic plasma cells
Prognosis of Multiple Myeloma
Median survival of 2-4 years with tx
10% 5-year survival
Waldenstrom's Macroglobulinemia
Malignant proliferation of PLASMACYTOID LYMPHOCYTES (Lymphoplasmacytic lymphoma)
IgM paraprotein causes HYPERviscosity of blood

*Uncontrolled clonal proliferation of terminally differentiated B lymphocytes
Diagnosis of Waldenstrom's Macroglobulinemia
1) IgM > 5g.dL
2) Bence Jones proteinuria (10%)
3) Absence of bone lesions
Clinical features of Waldenstrom's Macroglobulinemia
1) Lymphadenopathy
2) Splenomegaly
3) Anemia
4) Abnormal bleeding
5) Hyperviscosity syndrome (IgM)
Treatment of hyperviscosity syndrome in Waldenstrom's Macroglobulinemia
1) Chemotherapy
2) Plasmapheresis
Monoclonal Gammopathy of Undetermined Significance (MGUS)
Asymptomatic cousin of multiple myeloma
IgG spike <3.5 g
<10% plasma cells in BM
<1 g/day of Bence Jones proteinuria

*No tx necessary; close observation
Age distribution of Hodgkin's Disease
1) 15 - 30
2) >50

*Bimodal distribution
4 Histologic types of Hodgkin's Disease
1) Lymphocyte predominance (many B cells, few Reed Sternberg cells)
2) Nodular sclerosis (Reed Sternberg cells in collagen)
3) Mixed cellularity (Reed Sternberg cells in pleomorphic background)
4) Lymphocyte depleted (worst prognosis)
Ann Arbor Staging of Hodgkin's Disease
Stage I: single LN
Stage II: 2 or more LNs on same side of diaphragm
Stage III: both sides of diaphragm involved
Stage IV: disseminated disease

*Suffixes: A = no symptoms, B = fever, weight loss, night sweats
Clinical feature of Hodgkin's Disease
Painless LNPathy

*Supraclavicular, cervical, axillary, mediastinal nodes
Diagnosis of Hodgkin's Disease
1) LN biopsy - Reed Sternberg cells required
2) Presence of inflammatory cell infiltrates (plasma cells, eosinophils, fibroblasts, lymphocytes)
3) CXR, CT (chest & abdomen)
4) BM biopsy
Treatment of Hodgkin's Disease
Chemotherapy and radiation to involved field

*Stages 1, 2, & 3a: Radiotherapy alone
*Stages 3b, 4: Chemotherapy
Risk factors for Non-Hodgkin's Lymphoma (NHL)
2) Immunosuppression
3) Viral infections (EBV, HTLV-1)
4) H. pylori gastritis
5) Autoimmune disease (Hashimoto's thyroiditis, Sjogren's syndrome)
Clinical features of NHL
1) LNPathy (rapid enlargement)
2) Hepatosplenomegaly, abdominal pain, fullness
3) Recurrent infections, anemia, thrombocytopenia (BM involvement)
Diagnosis of NHL
1) LN biopsy (any LN >1cm present for more than 1 month)
2) Other tests: CXR (hilar or mediastinal adenopathy), CT, LDH and Beta-2 microglobulin, LFTs, CBC, CMP, BM biopsy)
CHOP Therapy
C: Cyclophosphamide
H: Hydroxydaunomycin
O: Oncovin (Vincristine)
P: Prednisone

*Used in Tx of NHL
Translocation associated with Follicular Lymphoma

*Bcl-2 on chromosome 18 gives fusion protein anti-apoptotic abilities
Translocation associated with Burkitt's Lymphoma
Sezary Syndrome
T-cell lymphoma of skin and bloodstream
Neoplastic proliferation of abnormal WBCs
--> Interfere w/ production of normal WBCs, RBCs, and platelets
Classification of Leukemia
Depends on type of WBC affected:
Granulocytes or monocytes: Myelogenous leukemia
Lymphocytes: Lymphocytic leukemia
Clinical features of leukemia
1) Anemia
2) Increased bacterial infections (neutropenia)
3) Mucosal or cutaneous bleeding (thrombocytopenia)
4) Splenomegaly, hepatomegaly, LNPathy
5) Bone & joint pain
6) Neurologic dysfunction (CNS involvement)
Electrolyte abnormalities seen in leukemia
1) Hyperuricemia
2) Hyperkalemia
3) Hyperphosphatemia
Tumor Lysis Syndrome
Potential complication of chemo seen in acute leukemia and high-grade NHL
Rapid cell death releases intracellular contents -->
HYPERkalemia, HYPERuricemia, HYPERphosphatemia

*Medical emergency
Polycythemia Vera
Malignant proliferation of hematopoietic stem cells --> excessive RBC production

*Median survival = 9-14 years
Clinical features of Polycythemia Vera
1) Hyperviscosity symptoms - HA, dizziness, weakness, pruritus, dyspnea
2) Thrombotic phenomena - DVT, CVA, MI, portal vein thrombosis
3) Bleeding
4) Splenomegaly, hepatomegaly
5) HTN
MC malignancy in children under 15

*This is the leukemia most responsive to therapy
MC leukemia after age 50
Chronic lymphocytic leukemia
Auer Rods are seen in which cancer?
Acute myelogenous leukemia
Chronic Lymphocytic Leukemia (CLL)
Monoclonal proliferation of lymphocytes that are morphologically mature but FUNCTIONALLY DEFECTIVE --> Do not become plasma cells

*Least aggressive leukemia
*WBCs: 50 - 200
Peripheral blood smear in CLL
1) Absolute lymphocytosis - mature WBCs
2) Smudge cells (cells "beaten up" in blood)
Medical treatment of CLL
1) Fludarabine
2) Chlorambucil
Chronic Myelogenous Leukemia
Neoplastic proliferation of myeloid stem cells
Indolent course becomes acute --> Blast Crisis
Translocation: t(9,22) Philadelphia Chromosome
*Average survival - 3 years
Cells of Myeloid lineage
1) Granulocytes
2) Erythrocytes
3) Platelets
Treatment of CML
Chemotherapy (antimetabolites or alkylating agents) may control chronic phase
*Blast crisis usually terminal
H/H in Polycythemia Vera
Usually above 50
Treatment of Polycythemia Vera
1) Repeated phlebotomy
2) Hydroxyurea or Recombinant Interferon Alpha (Myelosuppression)
Major criteria for Polycythemia Vera
1) Elevated RBC mass (men >36, women >32)
2) Arterial oxygen saturation >92%
3) Splenomegaly
Minor criteria for Polycythemia Vera
1) Thrombocytosis (>400)
2) Leukocytosis (>12)
3) Leukocyte alkaline phosphatase >100 (w/o fever or infection)
4) Serum vitamin B12 >900 pg/ml
Myelodysplastic Syndromes
Acquired clonal blood disorders
Ineffective hematopoiesis
Apoptosis of myeloid precursors
Pancytopenia despite normal BM
*Poor prognosis - progresses to acute leukemia
Bone Marrow in Myelodysplastic Syndromes
Dysplastic marrow cells with blasts or ringed sideroblasts

*Can progress from sideroblastic anemia
Treatment of Myelodysplastic Syndromes
RBC and platelet transfusions
Vitamin supplementation - B6, B12, folate

*BM transplant is only cure
Essential Thrombocytosis
Platelet count > 600,000/mm^3
Manifested by thrombosis
HYPOgranular, abnormally-shaped platelets
Treatment of Essential Thrombocytosis
1) Anti-platelet agents (Anagrelide, low-dose aspirin)
2) Hydroxyurea
Agnogenic Myeloid Metaplasia with Myelofibrosis
Fibrosis of BM --> Pancytopenia and extramedullar hematopoiesis

*Teardrop cells on peripheral smear are hallmark feature