Hematologic Diseases and Neoplasms Flashcards
Causes of aplastic anemia
- Idiopathic
- Radiation
- Medications (chloramphenicol, sulfonamides, gold, and carbamazapine)
- Viral infections (parvovirus, hep B and C, EBV, CMV, HZV, HIV)
- Chemicals (benzene and insecticides)
Aplastic anemia treatment
Bone marrow transplantation
Transfusion of PRBC or platelets
Vitamin B12
- converts homocysteine to methionine
- converts methylmalonyl CoA to succinyl CoA
- Stored in liver
Neurologic effects of B12 deficiency
- Demylination of the posterior columns, lateral corticospinal tract, and spinocerebellar tract (loss of position/vibratory sensation in the lower extremities, ataxia, and upper motor neuron signs)
- Urinary and fecal incontinence
- Dementia
Schilling test
- Give IM dose of unlabeled B12 to saturate binding sites
- Give oral dose of radioactive B12 and then measure the serum and urine levels to determine absorption
- Repeat the test (oral radioactive B12) with the addition of intrinsic factor.
Causes of folate deficiency
- Inadequate dietary intake
- Alcoholism
- Long-term oral antibiotics
- Increased demand
- Pregnancy
- Hemolysis
- Methotrexate
- Phenytoin
- Hemodialysis
- most common cause of megaloblastic anemia in alcoholics.
Hemoglobinuria
intravascular hemolysis
extravascular hemolysis - Peripheral smear
helmet cells and spherocytes
G6PD - peripheral smear
Heinz bodies
Haptoglobin in hemolytic anemia
low because it binds to hemoglobin (which is being destroyed)
Hemolytic signs of sickle cell anemia
- jaundice, pallor
- pigmented gallstones
- high output CHF
- aplastic crisis
Veno-occlusive signs of sickle cell anemia
- bone infarction
- hand-and-foot syndrome (dactylitits - avascular necrosis of the metacarpal and metatrasal bones)
- acute chest syndrome - recurrent pulmonary infarction
- splenic infarction
- avascular necrosis of joints - esp hips and shoulders
- priapism - vaso-occlusion of the penis
- CVA
- Opthalmologic - retinal infarcts, vitreous hemorrhage, proliferative retinopathy, retinal detachment
- Renal papillary necrosis
- chronic leg ulcers - esp over left lateral malleolus
- Abdominal crisis
Treatment for priapism
hydralazine, nifedipine, or silbestrol (antiandrogen)
Splenic sequestration crisis
pooling of blood in the spleen leading to splenomegaly and hypovolemia
Sickle cell anemia treatment
- Hydroxyurea - increases HbF (chronic)
- Fluids, morphine, warmth, and oxygen (acute)
- Blood transfusion in CLINICALLY unstable pts
- folate supplements
- penicillin prophylaxis 4mo-6yrs
- vaccines against encapsulated organisms
- bone marrow transplant
Hereditary spherocytosis
- Autosomal dominant defect in genes for spectrin, ankyrin, and other RBC membrane proteins
- Loss of RBC membrane
- Extravascular hemolysis by spleen
- RBC osmotic fragility test (acidified glycerol lysis test)
- Abnormal eosin-5 maleimide binding test
- Elevated reticulocyte count and MCHC
- Treat with splenectomy
- At risk for aplastic crisis and pigmented gallstones
- Common in Northern Europeans
- Jaundice and splenomegaly due to RBC getting trapped and hemolyzing in the splenic fenestrations.
- Hemoglobinuria.
G6PD Deficiency
- X-linked autosomal recessive
- G6PD is an enzyme that creates NADPH, a cofactor required to create glutathione
- Causes build-up of H2O2 which causes precipitation of HGB as Heinz bodies (leads to bite cells)
- Precipitated by drugs (nitrofurantoin, sulfonamides, primaquin, dimercaperol) and infection.
- Mild form involves only old RBC (AA); severe form (Mediteranean)
- Deficient NADPH formation on G6PD assay and reduced G6PD.
- G6PD may be normal during an acute attack.
Monoclonal gammopathy of undetermined significance
Asymptomatic, premalignant condition that can progress to multiple myeloma (20%)
Diagnosis: IgG spike
Multiple Myeloma
General characteristics: enormous amounts of monoclonal immunoglobulins (IgG or IgA)
- More common in African Americans
Clinical features: CRAB (calcium, renal, anemia, bone pain)
- bone pain in lower back, ribs and jaw
- recurrent infections (pneumonia and UTI most common cause of death)
- Anemia
- Renal failure
- Elevated beta-2 microglobulin
- Cord compression due to plasmacytoma or bone fragment (get MRI and starts steroids)
Diagnosis:
at least 10% abnormal plasma cells in the bone marrow + 1 of the following:
- M protein in the serum >/= 3g/dL
- M protein in the urine
- Lytic bone lesions (predominantly in the skull and axial skeleton)
- Get serum and urine electrophoresis
- Hypercalcemia, elevated total protein, elevated ESR, rouleaux formation on peripheral smear, pancytopenia
Treatment: hematopoeitic cell transplantaion is best, chemo is reserved for those not able to do HCT, radiation is palliative
Waldestrom’s macroglobulinemia
- Malignant proliferation of plasmacytoid lymphocytes that produce IgM.
Diagnosis: IgM>5g/dL, Bence Jones proteinuria, and no lytic bone lesions
- Lymphadenopathy, neurologic symptoms, splenomegaly, anemia, abnormal bleeding, and hyperviscocity, night sweats, headache, dizziness, visual problems, demyelinating sensorimotor neuropathy
Treatment: none, use chemo and plasmaphoresis to control hyperviscocity
Intravascular hemolysis
- Microangiopathic hemolytic anemia
- transfusion reactions
- Infections (clostridial species)
- paroxysmal nocturnal hemoglobinuria
- IV Rho(D) immune globulin infusion
Extravascular hemolysis
- Intrinsic RBC enzyme deficiencies
- Hemoglobinopathies (sickle cell anemia, thalassemia)
- Membrane defects
- Hypersplenism (IV immunoglobulin infusion)
- Warm or cold agglutinin autoimmune hemolytic anemia
- Infections (malaria, Bartonella)
Idiopathic thrombocytopenic purpura
- Due to IgG autoantibodies against the platelet membrane glycoproteins
Clinical presentation: previous viral infection, bruising and bleeding
Labs: isolated thrombocytopenia, peripheral smear w/ megakaryocytes and no other abnormalities
Treatment: children with skin manifestations only - observation
Children with bleeding - IVIg or steroids
Adults with platelets >/=30,000 w/o bleeding - observation
Adults with platelets
Bernard-Soulier syndrome
- Autosomal recessive
- Absent platelet glycoprotein Ib-IX-V (receptor for von Willebrand factor)
- mild thrombocytopenia w/ giant platelets, severe platelet dysfunction, and bleeding out of proportion with the thrombocytopenia
Chronic lymphocytic leukemia
- B cell disease
- “smudge cells” on blood smear due to increased fragility
- lymphadenopathy, lymphocytosis with small, mature-appearing lymphocytes
- Infection is most common cause of death
Staging: 0 lymphocytosis only - good I lymphocytosis + adenopathy - fair II splenomegaly - fair III Anemia - intermediate IV Thrombocytopenia - poor
Treatment: chlorambucil and prednisone
Hairy cell leukemia
- B lymphocyte chronic leukemia
- bone marrow tends to become fibrotic
- Stains + for TRAP (tartrate resistant acid phosphatase)
Treatment: cladribine (can cause neuro and kidney damage)
Phagocytosis in the spleen
- BBP enter the spleen via the splenic a. and are phagocytosed by dendritic cells in the white pulp
- Dendritic cells present antigens in association with MHC II to Th cells, activating them.
- Activated Th cells migrate to the marginal zone of the spleen where they come into contact with B cells in primary follicles.
- B cell activation causes secondary follicles to form with plasma-cell rich germinal centers.
- Antibodies then enter the circulation and bind their specific antigen, facilitating phagocytosis by opsonization.
Chronic granulomatous disease
X-linked or autosomal recessive defect in NADPH oxidase that causes defective intracellular killing
Severe combined immune deficiency
autosomal recessive defect in adenosine deaminase leading to decreased numbers of circulating lymphocytes
Leukocyte adhesion defect
Impaired chemotaxis due to an autosomal recessive defect in integrin beta 2
DiGeorge syndrome
thymic aplasia due to deletion of chromosome 22 which causes defective cell-mediated immunity
Anaphylactic transfusion reaction
rapid onset shock, angioedema, urticaria, and respiratory distress
- Begins seconds to minutes following transfusion
- Cause by recipient anti-IgA antibodies
Treatment: IM epinephrine, mechanical ventilation, histamine blockers and glucocorticoids
- Give pts washed cell products in the future
Transfusion-related acute lung injury
- respiratory distress and signs of noncardiogenic pulmonary edema
- within 6 hours of transfusion
- caused by donor anti-leukocyte antibodies
Primary hypotension reaction
- Transient hypotension in pts taking ACE inhibitors
- Within minutes of transfusion
- Caused by bradykinin in blood products
Bacterial sepsis
- fever, chills, septic shock and DIC
- minutes to hours after transfusion
B12 deficiency anemia
- Loss of intrinsic factor due to gastric resection or autoimmune gastritis are common causes
- Cofactor in demethylation of CH3-THF to THF which is necessary for formation of thymidylate and purines.
- Can present as hemolytic anemia due to hemolysis of immature RBCs.
Thrombotic thrombocytopenic purpura
- Decreased ADAMTS13 von Willebrand cleaving factor protease (shown on flow cytometry).
- Hemolytic anemia, thrombocytopenia, renal failure, altered mental status, and fever.
- Idiopathic, drug toxicity, or HIV as causes
- Peripheral blood smear will almost always show schistocytes.
- Treat with plasmapheresis
Anemia in ESKD
- Erythropoeitin causes a surge in iron usage which can change anemia of chronic disease into iron-deficiency anemia.
- Treatment of choice in dialysis patients is IV iron dextran.
Hemophilias
Intramuscular hematomas, GI or GU bleeding
- Normal platelet count, bleeding time and PT time.
- Prolonged PTT.
Causes of macrocytic anemia
- folate deficiency
- B12 deficiency
- Myelodysplastic syndromes
- AML
- Drugs (hydroxyurea, zidovudine, chemo agents)
- Liver disease
- Alcohol
- Hypothyroidism
Paroxysmal nocturnal hemoglobinuria
- absent CD55 (protects the RBC membrane from destruction by complement).
Causes of thrombocytopenia
- Viral infections (EBV, HIV, Hep C)
- Chemo
- Myelodysplasia
- Alcohol
- Congenital (Fanconi syndrome)
- vitamin B12 or folate deficiency
- SLE
- Medications (heparin)
- ITP, TTP
- intravascular coagulation, HUS
- anti-phospholipid syndrome
- Dilutional
- Splenic sequestration
- ALWAYS test for hep C and HIV
Carbon monoxide poisoning
Symptoms: headache, dizziness, nausea, polycythemia
Type 2 heparin induced thrombocytopenia
- Heparin binds platelet factor 4, this complex triggers IgG antibodies which bind to it. This whole complex then activates platelets by binding to the Fc receptors on the platelets.
- Spleen removes these platelet complexes.
- Complexes activate adjacent platelets causing thrombosis.
- End-result: thrombocytopenia, arterial and venous thrombosis.
Treatment of hypercalcemia
Immediate: fluid hydration and calcitonin, avoid loop diuretics
Long-term: bisphosphonates (zoledronic acid)
Leukomoid reaction
- Increased leukocyte alkaline phosphatase
- Severe infection
- Can have associated immature neutrophils
Drugs causing megaloblastic anemia
- Phenytoin, primidone, and phenobarbitol impair folic acid absorption in the small intestine.
- Trimethoprim and methotrexate are dihydrofolate reductase inhibitors.
Trousseau’s syndrome
- Hypercoagulability disorder which presents with recurrent and migratory superficial thrombophlebitis at unusual sites
- Associated with occult visceral malignancy - pancreatic, stomach, lung, or prostate cancer.
Hypercalcemia
- typically seen at >12mg/dL
- Constipation, anorexia, vomiting, weakness, polyuria, confusion, and lethargy.
- Can also cause acute pancreatitis.
Rivaroxiban
Direct factor Xa inhibitor
- Effective in 2-4 hours
Androgen abuse
- LVH, decreased HDLand increased LDL, polycythemia, hypercoagulability, hepatotoxicity
Basophilic stipiling
- Can be due to lead poisoning, but also alcoholism and thalassemia.
- Nonspecific.
Polycythemia vera
Symptoms: facial plethora, peptic ulcers (histamine release), and gouty arthritis (increased cell turnover)
- Expanded blood volume leads to hypertension.
Treatment: phlebotomy
Hyposthenuria
Impaired ability of the kidneys to concentrate the urine
-Seen in sickle cell anemia when RBC sickle in the vasa recta of the inner medulla, impairing countercurrent exchange and free water reabsorption.
Increasing appetite in cancer patients
- Progesterone analogs (megestrol acetate and medroxyprogesterone acetate)
- Corticosteroids (more side effects)
- TCA (mirtazapine [Remeron])
Homocysteine and DVT’s
- Highly reactive amino acid.
- Predisposes to atherosclerosis and DVT.
- Causes direct vascular damage, activation of clotting mechanisms, and inhibition of antithrombotic pathways.
- Levels can be normalized by administration of pyridoxine and folate.
- Vitamin B6, B12 and folate are all cofactors in homocysteine breakdown.
- B6 is a cofactor that works with the cystathionine beta-synthetase enzyme to convert homocysteine into cystathionine.
Clopidogrel
- used to prevent arterial thrombosis, but not venous thrombosis.
Infectious mononucleosis
Heterophile antibodies can be negative early on and then become positive
- Palatal petechiae, maculopapular rash.
Pernicious anemia
- Associated with atrophic gastritis with decreased production of intrinsic factor by gastric parietal cells
- Increased risk of intestinal-type gastric cancer and gastric parietal cells.
- Monitor stool for blood.
Febrile non-hemolytic
- Fever and chills within 1-6 hours of transfusion
- Caused by cytokines in the blood products
- Uses leukoreduced blood products.
Acute hemolytic
- Fever, flank pain, hemoglobinuria, renal failure, and DIC
- Within 1 hour of transfusion
- positive direct Coombs
- ABO incompatibility
Delayed hemolytic
- Mild fever and hemolytic anemia
- 2-10 days after a transfusion.
- Positive direct Coombs test and positive new antibody screen.
- Anamnestic antibody response.
