Heme:Onc Path Flashcards
- Symptoms: Leukocoria, increased risk of osteosarcoma. Lab Values: *13q RB tumor supressor gene deletion. Pseudorosettes. * Pathophysiology: *Autosomal dominant. RB regulates G1 to S transition.
Retinoblastoma
- Symptoms: Abdominal mass; myelopathy (spinal cord compression), treatment resistant diarrhea (VIP secretoin), Horner’s syndrome, opsoclonus myoclonus syndrome, ataxia hypertension. Lab Values: 1p N-myc oncogene amplification. HVA (a breakdown product of dopamine) in urine. Pseudorosettes. Bombesin positive. Pathophysiology: The most common tumor of the adrenal medulla in children. Can occur anywhere along the sympathetic chain. Treatment: *Cyclophosphamide
Neuroblastoma
- Symptoms: Granulomatous vasculitis with eosinophilia. Most often presents with ASTHMA, sinusitis, skin lesions, and peripheral neuropathy (e.g., wrist/foot drop, extreme pain); can also involve heart, GI, and kidneys.* Lab Values: 17p p53 tumor supressor gene deletion. Pathophysiology: *Autosomal dominant
Li-Fraumeni syndrome
- Symptoms: Breast and ovarian cancer Lab Values: 17q/13q tumor supressor gene deletion. Pathophysiology: *Autosomal dominant
BRCA1/2
- Symptoms: Colon becomes covered with adenomatous polyps after puberty. Progresses to colon cancer unless resected. Associated with osteomas. Lab Values: 5q APC tumor supressor deletion. Pathophysiology: Autosomal dominant Treatment: *
Familial adenomatous polyposis
- Symptoms: Female with menstural bleeding, uterine leiomyoma (fibroids). Male with GI bleed. Dysphagia, koilonychia (spoon fingernails). Lab Values: *Microcytic, hypochromatic. Decreased serum iron, decreased ferritin, increased TIBC.
Iron deficiency anemia
- Symptoms: Asians or Africans. 1-2 deletions asymptomatic. 3 deletions results in HbH disease. 4 deletions results in hydrops fetalis. Lab Values: Microcytic, hypochromatic. Target cells. Pathophysiology: *HbH = 4 beta chains; Hb Barts = 4 gamma chains
Alpha-thalassemia
- Symptoms: Mediterraneans. Heterozygote asyptomatic. Homozygote has severe anemia. Bone marrow expansion leads to Chipmunk facies (skeleton deformities). Lab Values: Microcytic, hypochromatic. “Crew cut” appearance of skull on X-ray. Increased HbA2 and HbF. Target cells. Pathophysiology: Point mutations in splicing sites and promoter sequences. Repeat transfusions leads to secondary hemochromatosis. Treatment: *Transfusions
Beta-thalassemia
- Symptoms: Microcytic anemia, GI and kidney disease. Mental deterioration in children and memory loss & demyelination in adults. Lab Values: Microcytic, hypochromatic. Basophilic stippling. Increased protoporphyrins. Pathophysiology: *Inhibits ferrochelatase and ALA dehydratase leading to decreased heme synthesis.
Lead poisoning
- Symptoms: Skin paleness, fatigue, dizziness and hepatosplenomegaly. Heart disease, liver damage and kidney failure can result from iron buildup. Lab Values: Microcytic, hypochromatic. Increased serum iron, normal TIBC, increased ferritin. Ringed sideroblasts (iron laden mitochondria). Pathophysiology: X-linked defect in delta-aminolevulinic acid synthase or due to lead/alcohol. Treatment: *Pyridoxine (B6) therapy
Sideroblastic anemia
- Symptoms: Megaloblastic anemia, glossitis. Lab Values: *Macrocytic, hyperchromatic. Hypersegmented neutrophils, increased homocysteine, normal methylmalonic acid.
Vitamin B9 (Folate) deficiency
- Symptoms: Megaloblastic anemia, glossitis, subacute combined degeneration. Lab Values: Macrocytic, hyperchromatic. Hypersegmented neutrophils, increased homocysteine, increased methylmalonic acid. Pathophysiology: *Caused by Diphyllobothrium latum, Crohn’s disease, pernicious anemia, gastrectomy, malnutrition.
Vitamin B12 deficiency
- Symptoms: ** Lab Values: *Macrocytic, hyperchromatic. * Pathophysiology: *Caused by liver disease, alcoholism, reticulocytosis, metabolic disorder (orotic aciduria), 5-FU, AZT, hydroxyurea
Nonmegaloblastic macrocytic anemia
- Symptoms: ** Lab Values: Normocytic, normochromatic. Decreased iron, decreased TIBC, increased ferritin (acute phase protein!) Pathophysiology: *Chronic inflammation elevates hepcidin leading to decreased iron release from macrophages.
Anemia of chronic disease
- Symptoms: No hepatosplenomegaly. Pancytopenia characterized by severe anemia, neutropenia, and thrombocytopenia. Lab Values: Normal cell morphology, but hypocellular bone marrow with fatty infiltration. Pathophysiology: *Caused by radiation, drugs (chloramphenicol, benzene, alkylating agents), viruses (parvovirus B19, EBV, HIV), Fanconi’s anemia, acute hepatitis.
Aplastic anemia
- Symptoms: Small round RBCs with no central pallor. Splenomegaly, aplastic crisis with B19. Lab Values: Normocytic, normochromatic. Increased MCHC, increased RDW. Positive osmotic fragility test. Pathophysiology: Defect in RBC membrane skeleton proteins (ankyrin, band 3.1, spectrin). Increased Howell-Jolly bodies after splenectomy. Treatment: *Splenectomy
Hereditary spherocytosis
- Symptoms: Hemolytic anemia following oxidant stress (sulfas, infections, fava beans). Lab Values: Normocytic, normochromatic. Heinz bodies and bite cells. Pathophysiology: *X-linked recessive. Decreased gluthione synthesis.
G6PD deficiency
- Symptoms: Hemolytic anemia in a newborn. Lab Values: Normocytic, normochromatic. Rigid RBCs due to decreased ATP. Pathophysiology: Autosomal recessive. Treatment: *
Pyruvate kinase deficiency
- Symptoms: Newborns asymptomatic (due to HbF). Salmonella osteomyelitis, autosplenectomy, aplastic crisis (B19), avascular necrosis, resistance to malaria. Non-healing ulcers. Lab Values: Normocytic, normochromatic. “Crew cut” skull on x-ray due to bone marrow expansion. Decreased serum haptoglobin. Decreased ESR. Systolic ejection murmur at right 2nd intercostal space. Pathophysiology: Autosomal recessive. Misense mutation (substitution of normal glutamic acid with valine). Treatment: *Hydroxyurea
Sickle cell anemia
- Symptoms: Mild sickle cell anemia when combined with HbS (HbS/C) Lab Values: *Normocytic, normochromatic.
HbC defect
- Symptoms: Intravascular hemolysis (blood in morning void), hepatic vein thrombosis, abdominal pain. Lab Values: Ham’s (sucrose) test. Increased urine hemosiderin. Pathophysiology: *Complement-mediated hemolysis due to impaired synthesis of GPI anchor/decay-accelerating factor (CD55/CD59)
Paroxysmal nocturnal hemoglobinuria
- Symptoms: Widespread activation of clotting leads to a deficiency in clotting factors, which creates a bleeding state. Lab Values: Schistocytes (helmet cells), increased LDH. Decreased PC and fibrinogen. Increased BT, PT, PTT, TT, d-dimers. Pathophysiology: Caused by sepsis, trauma, obstetric complications (placenta is rich in tissue factor), acute pancreatitis, malignancy, transfusion. Treatment: *Dialysis.
Diffuse intravascular clotting (DIC)
- Symptoms: Microthrombosis, miroangiopathic hemolytic anemia, neurologic symptoms, renal symptoms, thrombocytopenia, fever. Lab Values: Decreased PC, increased BT. Normal PT, PTT, and TT. Pathophysiology: *Deficiency of ADAMTS 13 (vWF metalloprotease).
Thrombotic thromocytopenic purpura (TTP)
- Symptoms: Ingestion of raw meat followed by bloody diarrhea. Renal failure, microangiopathic hemolytic anemia, microthrombosis, less pronounced neurological symptoms. Lab Values: Schistocytes (helmet cells), increased LDH. Decreased PC, increases BT. Normal PT, PTT, and TT. Pathophysiology: *O157:H7 (enterohemorrhagic) E. coli.
Hemolytic uremic syndrome (HUS)
- Symptoms: Epistaxis, petechia, purpura. Lab Values: Decreased PC, increased BT. Normal PT, PTT, and TT. Pathophysiology: *Defect in Gp1b
Bernard-Soulier disease
- Symptoms: Epistaxis, petechia, purpura. Lab Values: Normal PC, increased BT. Normal PT, PTT, and TT. Pathophysiology: Defect in GpIIb/IIIa Treatment: *
Glanzmann’s thrombasthenia
- Symptoms: Epistaxis, petechia, purpura following an acute viral infection. Lab Values: Megakaryocytosis. Deceased PC, increased BT. Normal PT, PTT, and TT. Pathophysiology: *Autoimmune; anti-GpIIb/IIIa antibodies leading to platelet destruction.
Idiopathic thrombocytopenic purpura (ITP)
- Symptoms: Hemarthrosis, bleeding on circumcision, epistaxis, bleeding on cutting teeth. Lab Values: Normal PC. Increased PTT. Normal BT, PT, TT. Pathophysiology: *Deficiency of Factor VIII. X-linked recessive.
Hemophilia A
- Symptoms: Hemarthrosis, bleeding on circumcision, epistaxis, bleeding on cutting teeth. Lab Values: Normal PC. Increased PTT. Normal BT, PT, TT. Pathophysiology: *Deficiency of Factor IX. X-linked recessive.
Hemophilia B
- Symptoms: Neonate with hemorrhage, warfarin use, or following broad-spectrum antibiotics in adult. Lab Values: Decreased factors II, VII, IX, X, protein C, and protein S. Increased PT, PTT. Normal BT Pathophysiology: *Neonates have sterile intestines and are unable to synthesize vitamin K.
Vitamin K deficiency
- Symptoms: Mild. Epistaxis, bleeding following dental procedures. Most common bleeding disorder. Lab Values: Increased PTT (due to decreased factor VIII), increased BT. Normal PT, TT, PC. Failure to aggregate with ristocetin. Pathophysiology: Autosomal dominant. Treatment: *Desmopressin (DDAVP).
von Willebrand’s disease
- Symptoms: Kidney failure Lab Values: *Increased BT. Normal PT, PTT, TT, PC.
Uremia
- Symptoms: Hypercoagulability leading to DVTs and pulmonary embolism. Lab Values: Low PTT that is not corrected with addition of Protein C Pathophysiology: *Mutated factor V is resistant to degradation by protein C.
Factor V Leiden
- Symptoms: Hypercoagulability leading to DVTs and pulmonary embolism. Lab Values: ** Pathophysiology: *Gene mutation in prothrombin 20210A, leading to increased gene expression of prothrombin.
Prothrombin gene mutation
- Symptoms: Hypercoagulability leading to DVTs and pulmonary embolism. Lab Values: Reduced increase in PTT after administration of heparin. Pathophysiology: ** Treatment: *
Antithrombin III deficiency
- Symptoms: Hypercoagulability leading to DVTs and pulmonary embolism. Hemorrhagic skin necrosis following administration of warfarin. Lab Values: ** Pathophysiology: *Decreased inactivation of Va and VIIIa.
Protein C or S deficiency
- Symptoms: Neonatal hemolysis due to Rh or other blood group incompatiblity; mother’s antibodies attack fetal RBCs. Lab Values: *Combs positive
Erythroblastosis fetalis
- Symptoms: Autoimmune hemolytic anemia Lab Values: Combs positive Pathophysiology: *IgG antibodies. Due to SLE, CLL, or methyldopa
Warm aggultinins
- Symptoms: Autoimmune hemolytic anemia Lab Values: Combs positive Pathophysiology: *IgM antibodies. Due to Mycoplasma pneumoniae, infectious mononucleosis (CMV, EBV).
Cold agglutinins
- Symptoms: Thromobocytopenia, hypercoagulability following heparin administration. Lab Values: ** Pathophysiology: *Autoimmune disease. Antibodies to platelet factor IV-heparin complex.
Heparin induced thrombocytopenia