UWorld Heme/Onc Flashcards
This is a lymphoplasmocytic malignancy characterized by the excessive production of monoclonal IgM antibody
Waldesnstrom macroglobulinemia
Bone marrow biopsy in Waldenstrom macroglobulinemia
->10% clonal B cells
What are common consequences of elevated serum IgM in patients with Waldenstrom macroglobulinemia?
- Hyperviscosity syndrome
- neuropathy
- cryoglobulinemia
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder driven by the abnormal fusion of what genes on what chromosomes?
-This gene causes leukomogenesis due to what constitutively enzyme?
- BCR-ABL (translocation between chromosomes 9 and 22)
- Tyrosine kinase (first line treatment tyrosine kinase inhibitors such as imatinib)
main lab finding in CML
dramatic leukocytosis (often > 100,000)
Mutation in Polycythemia vera?
JAK2
Treatment of Polycythemia vera?
- Phlebotomy
- Hydroxyurea (If increased risk of thrombus)
For patients with a DVT/PE and on warfarin, the warfarin dose is typically adjusted to achieve a therapeutic INR values of what?
between 2 and 3
Clinical features of Thrombotic thrombocytopenia purpura (TTP)
- Hemolytic anemia (Increased LDH, decreased haptoglobin) with schistocytes
- Thrombocytopenia (high Bleeding time, normal PT/PTT)
- Sometimes: renal failure, neurologic, fever
Pathophys of TTP
low ADAMTS13 –> uncleaved vWF multimers –> platelet trapping and activation
Management of TTP
- Plasma exchange
- Glucocorticoids
- Rituximab
- Thrombocytopenia
- microangiopathic hemolytic anemia
- renal insufficiency
- neurologic changes
- fever
- Classic pentad of what
TTP
what lab values are due to microangiopathic hemolytic anemia
-high indirect bilirubin, AST/ALT, LDH
Evidence of thrombocytopenia and microangiopathic hemolytic anemia should always raise suspicion for TTP . . what is a crucial test in the diagnostic workup?
What would it show?
- Peripheral blood smear
- signs of intravascular hemolysis (e.g. schistocytes, helmet cells, triangle cells)
how to diagnose Chronic lymphocytic leukemia?
- Severe lymphocytosis and smudge cells
- flow cytometry
- lymph node and bone marrow biopsy NOT generally needed
This is caused by autoantibodies to platelet factor 4 (PF4) complexed with heparin and is characterized by thrombocytopenia, arterial or venous thrombosis, and necrotic skin lesions at heparin injection sites within 5-10 days of therapy
Heparin-induced thrombocytopenia (HIT)
Most patients with Factor V leiden have an autosomal dominant point mutation in the gene for factor V that makes it unable to respond to what?
activated protein C, an innate anticoagulant
PT and activated PTT times in Factor V leiden
-Can be normal as the major procoagulant effects are due to continued thrombin formation
Lab findings in Acute myeloid leukemia
- Cytopenias (leukocytes may be up, normal, or down)
- Elevated LDH
- Peripheral smear - usually myeloblasts with Auer rods
One unique type of AML is APML, which is characterized by life threatening coagulopathy due to what?
-DIC (prolonged PT/active PTT, HYPOfibrinogenemia)
Anaphylactive reactions to transfused blood products are characterized by rapid onset (within seconds to minutes) of respiratory distress and hypotension, which quickly progress to respiratory failure and shock. Individuals with what are at increased risk and why?
-IgA deficiency due to the presence of anti-IgA antibodies
- Bone marrow transplant in HLA-matched siblings
- Skin (maculopapular rash involving palms, soles, and face)
- intestine (blood-positive diarrhea)
- Abnormal liver function tests and jaundice
- What is the disease and pathophysiology?
- Graft-versus-host disease
- Activation of DONOR T lymphocytes
What are the clinical signs of type 2 heparin induced thrombocytopenia
Suspected with heparin exposre > 5 days and any of the following:
- Platelet count reduction >50% from baseline
- Arterial or venous thrombosis
- Necrotic skin lesions at heparin injection sites
- Acute systemic anaphylactoid reactions after heparin
What is the diagnostic evaluation in type 2 heparin-induced thrombocytopenia?
- Serotonin release assay: Gold standard confirmatory test
- Start treatment in suspected cases prior to confirmatory tests
Therapy in type 2 heparin induced thrombocytopenia
- Stop ALL heparin products
- Start a direct thrombin inhibitor (e.g. argatroban) or fondaparinux (synthetic pentasaccharide)
Describe the use of warfarin in HIT
- Warfarin is used for anticoagulation maintenance in patients with HIT but only after the patient has received another anticoagulant and the platelet count is >150k.
- Initial treatment with warfarin is contraindicated in patients with HIT as it rapidly lowers protein C levels, which may transiently increase the risk of thrombus
Malignancy is the most common cause of Superior vena cava syndrome. Lung cancer (particularly small cell lung cancer) and NHL are often implicated. Other possible causes include fibrosing mediastinitis (secondary to histoplasmosis or Tb infection) or thrombosis secondary to indwelling central venous devices. When the history and physical exam are suggestive, what imaging is warranted?
chest x-ray
mechanism by which B12 causes anemia?
-it is a required cofactor for the formation of thymidylate and purine molecules for DNA synthesis
Which cause of anemia works through impaired glutathione synthesis
-G6PD deficiency
Coombs test in Hereditary spherocytosis
negative
Autoimmune hemolytic anemia and hereditary spherocytosis both may show spherocytes without central pallor. What type of hemolytic anemia do they cause?
extravascular
coombs test in autoimmune hemolytic anemia
positive
Describe how antiphospholipid syndrome affects partial thromboplastin time (PTT)
- prolongs it as it binds to phospholipids used in most assays
- This is a laboratory artifact and does not correlate with bleeding in vivo
Describe the pathophysiology of megaloblastic anemia caused by phenytoin or other anti-epileptic drugs like primidone and phenobarbital
impaired absorption of FOLIC ACID in the small intestine
What drugs cause megaloblastic anemia due to antagonizing the physiologic effects of folic acid by inhibiting dihydrofolate reductase?
- Methotrexate
- Trimethoprim
Cholesterol embolization can occur due to plaque embolization into small arteries following coronary angiography. Cholesterol embolization classically causes what skin findings?
- livedo reticularis (mottled erythema)
- gangrene cyanosis
- mostly of lower extremities
patient with constipation, back pain, and lab evidence of anemia, renal insufficiency, and hypercalcemia likely has what?
multiple myeloma
A patient with multiple gunshot wounds in past who gets a fulminant infection likely has aplenia. They are at risk for infection with encapsulated baceria (e.g. strep pneumoniae and haemophilus influenza) due to what mechanism
deficits in antibody response and antibody-mediated phagocytosis/complement activation
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by the BCR-ABL fusion gene. It is marked by a dramatic leukocytosis, absolute basophilia, and a preponderance of early immature neutrophil precursors (promyelocytes, myelocytes). What score/test can help differentiate CML from leukemoid reaction?
- Leukocyte alkaline phosphatase (LAP) score
- Low in CML
- High in leukemoid reaction
Multiple myeloma should be suspected in elderly patients with laboratory finding of hypercalcemia, normocytic anemia, renal insufficiency, and a protein gap. Describe what a protein gap is and what it indicates?
- difference between total protein and albumin >4 g/dL
- indicates elevated nonalbumin protein in the serum; it may be seen with polyclonal gammopathies (infection, connective tissue disease) or excessive monoclonal protein (MM, Waldenstrom macroglobulinemiaia)
in MM, serum protein electrophoresis (SPEP) can determine if a protein gap is caused by a monoclonal or polyclonal source. In MM, SPEP typically shows and a monoclonal spike (M-spike). Diagnosis is then confirmed by bone marrow biopsy showing what? . . . peripheral blood smear would show what?
- > 10% clonal plasma cells
- rouleaux formation (stacking of red blood cells like coins)
clinical manifestations of MM
- Bone pain, fractures
- Constitutional symptoms (weight loss, fatigue)
- recurrent infections
Describe why patients with MM are prone to infection
- Neoplastic infiltration of the bone marrow alters and impairs the normal lymphocyte population, resulting in ineffective antibody production and hypogammaglobulinemia
- Respiratory (e.g. strep pneumo) and UTI most common
What lab findings can be present in anabolic steroid abuse
- erythrocytosis (dose dependent increases in hematocrit and hemoglobin)
- hepatotoxicity
- dyslipidemia
Treatment of TTP?
-plasma exchange
What is considered first line treatment for chemotherapy induced nausea?
Serotonin (5HT) receptor antagonists (e.g. ondansetron)
An acutely ill patient with underlying liver disease can become vitamin K deficient in how long?
7-10 days
Bone marrow biopsy is an invasive test and performed only after gathering more info with what?
- peripheral smear (rouleaux)
- serum free light chain analysis
- SPEP
- urine protein electrophoresis
Risk of Tumor Lysis Syndrome is due to initiation of cytotoxic chemotherapy. What are the manifestations?
- Severe electrolyte abnormalities
- Increase phosphorus, potassium, uric acid
- decrease calcium
- Acute Kidney injury (due to uric acid/calcium phosphorus)
- cardiac arrhythmias
what is the tumor lysis syndrome prophylaxis?
- IV fluids
- Allopurinol or rasburicase
Bone pain is a common presenting symptom in Multiple myeloma. In an elderly patient with evidence of osteolytic lesions on x-ray, MM should always be suspected. What is the screening test of choice?
How is it confirmed?
- Serum protein electrophoresis, urine protein electrophoresis, and free light chain analysis
- Diagnosis can be confirmed with bone marrow biopsy
x-ray showing an expansile eccentrically placed lytic area in the epiphysis of the distal femur is suggestive of what
Giant cell tumor . . . . “soap bubble appearance”
What is first line treatment of Giant cell tumor of the bone
-Surgery . . (e.g. intralesional curettage with or without bone grafting)
this is a rare condition most commonly due to hyperparathyroidism from parathyroid carcinoma. Osteoclastic resorption of bone leads to replacement with fibrous tissue (brown tumors) and causes pain.
Osteitis fibrosa cystica (von Recklinghausen disease of bone)
Describe imaging and location of Osteitis fibrosa cystica
-Subperiosteal bone resorption on the radial aspect of the middle phalanges, distal clavicular tapering, “salt and pepper” appearance of the skull, bone cysts, and brown tumors of the long bones
This appears as a sclerotic, cortical lesion on imaging with a central nidus of lucency. It typically causes pain that is worse at night and unrelated to activity. However, the pain is quickly relieved by NSAIDs
Osteoid Osteoma
What diets are particularly at risk of vitamin B12 deficiency
-Vegetarians, particularly if dairy product consumption is limited . . . vegans
in a patient with B12 and folic acid deficiency . . . maybe a vegan alcoholic . . replenishing folic acid without Vitamin B12 supplementation corrects the megaloblastosis but leads to what?
rapid progression of neurologic symptoms
Both folate and Cobalamin (B12) are cofactors in the conversion of what to what?
-homocysteine to methionine
what Bleeding lab value besides thrombocytopenia is suggestive of HIT
markedly elevated aPTT
What test is used to diagnose CLL
- Severe lymphocytosis and smudge cells
- Flow cytometry
- Lymph node and bone marrow biopsy NOT generally needed
hereditary telangiectasia (Osler-Weber-Rendu syndrome) is characterized by what 3 things?
- Diffuse telangiectasias
- Recurrent epistaxis
- widespread AV malformations
AV malformations in the lungs can cause what
- right to left shift
- chronic hypoxemia
- reactive polycythemia
Epidural spinal cord compression must be suspected in any patients with a history of malignancy who develops back pain with motor and sensory abnormalities. Bowel and bladder dysfunction are late neurologic findings. What should be given without delay
- IV glucocorticoids
- MRI is then recommended
Describe the Glucose-6-phosphate activity level in an individual with deficiency during an attack?
- may be normal
- Most erythrocytes that are severely G6PD deficient are hemolyzed early in a hemolytic episode, and reticulocytes which have normal G6PD levels, are circulating at abnormally high levels
- It is best to wait 3 months before retesting
Hard. unilateral, NON tender lymph nodes are always suspicious for cancer and must be evaluated immediately. In an older patient with a hx of smoking, such lymph nodes in the submandibular or cervical region are highly concerning for what?
- Head and neck cancer
- The vast majority of head and neck cancer is squamous cell carcinoma
