Step 2 Heme/Onc Flashcards
Heparin: MOA and Corresponding lab
Activates antithombin, therefore inhibiting thrombin and preventing conversion of fibrinogen to fibrin. Active in common pathway. Checked by checking PTT. Antidote is protamine sulfate. LMWH has more effect on factor Xa and LMWH does not increase PTT
Warfarin: MOA and Corresponding lab
Inhibits vitamin K epoxide reductase thereby inhibiting synthesis of K-dependent clotting factors II, VII, IX, X, C and S. Check lab with PT and INR. Therapeutic target for INR=2-3. Rapid reversal =FFP or Vitamin K. Warfarin is teratogenic
tPA: MOA and Corresponding lab
Aids conversion of plasminogen to plasmin, which breaks down fibrin. Increases PT and PTT. treat toxicity with aminocaproic acid
ApiXaban, and RivaroXaban: MOA and lab?
Factor Xa Inhibitors: PT/PTT not monitored. No reversal agent
LMWH (enox)
Mainly inhibits factor Xa. Antifactor Xa can be monitored but enox is typically not monitored. Protamine is less effective at reversal
Direct thrombin inhibitors (Dabigatran and argatroban)
Directly inhibits factor II/thrombin) No lab monitoring. Idaracizumab can reverse dabigatran.
3 types of hemophilia, deficient clotting factors. PDT
A: XIII, B: IX, C:XI. Pts will have elevated PTT. Best initial test: mixing study. Tx: factor replacement or desmopressin, which releases factor VIII from endothelial cells
VWD PDT
Autosomal defect or deficiency in platelets. Often presents in childhood with recurrent and mucosal bleeding. Lab: increased bleeding time. +/- increased PTT. PT and plt count will be NL. Most accurate test: Ristocetin cofactor assay (that will show decreased agglutination) and vWF antigen level. Tx: DDAVP. Note: ASA increases bleed risk in pts w VWD.
3 common hypercoaguable states?
Factor V leiden, HIT (a rapid 50% drop in PLTs), antiphospholipid syndrome.
How long do you treat pts a hypercoaguable state who have had a DVT or PT? With what?
heparin immediately, followed by 3-6 months of warfarin for first event. if second event, 6-12 months of warfarin, if 3rd, lifelong anticoag is needed.
Diagnstic clinical features of DIC?
Thrombosis and hemorrhage. DIC is an acquired coagulopathy caused by deposition of fibrin in small blood vessels leading to thrombosis and end-organ damage. Depletion of clotting factors and platelets leads to a bleeding diathesis. Common associations with DIC: OB complications, sepsis, neoplasms, acute promyelocytic leukemia, pancreatitis, hemolysis, vascular disorders (aortic aneurysm), massive trauma, drug reactions, acidosis and ARDS. DIC may be confused w liver disease but unlike liver dz, factor VIII is depressed.
Clinical presentation: acute: bleeding from venipuncture sites, bleeding into organs, ecchymoses and petichiae. Chronic: bruising and mucosal bleeding, thrombophelbitis, renal dysfunction, and transiend nrueologic syndromes.
TTP PDT. 5 sx that should be a tip off:
Deficiency of vWF-cleaving enzyme adamts-13, results in platelet microthrombi. RBCs are fragmented by contact w microthrombi, leading to hemolysis (microangiopathic hemolytic anemia). Maintain high suspicion if 3 out of 5 symptoms are present: FAT RN
1. Fever
2. Anemia: microangiopathic hemolytic anemia
3. Thromboytopenia
4. Renal changes
5. Neurologic Changes (delerium, seizure, stroke)
Clinical dx: presence of schistocytes.
Tx: plasma exchange. PLT transfusion is contraindicated as can worsen condition.
3 causes of micorangiopathic hemolytic anemia?
HUS, TTP and DIC
DDX for thrombocytopenia
HIT SHOC HIT or HUS ITP TTP or Treatment/meds Splenomegaly Hereditary (Wiskott-Aldrich Syndrome) Other (malignancy) Chemo
PDT for Immune thrombocytopenic purpura
ITP can accure follow a viral illness with abrupt onset of hemorrhagic complications. Commonly affects kids 2-6 yo. Chronically, there is insitious onset of sx or incidential thrombocytopenia. Affects adults 20-40 yo.
Diagnosis of exclusion. CPC, smear. If PLTs>30,000, and no bleeding, no tx necessary
If PLT<30m000 or bleeding: steroids or IVIG. Other tx if plt does not improve=ritux, splenectomy, or thrombopoietin receptor agnoist (romiplostim or eltrombopag).
Microcytic Anemia DDX:
TAILS: Thalassemias, ACD, Iron-deficiency, Lead, Sideroblastic
G6PD Deficiency triggers, best test, what will smear show?
G6PD deficiency leaves RBCs susceptible to hemolytic anemia, causing a normocytic anemia with increased retic. Common triggers: sulfa drugs, antimalarials, infections, fava beans. Best initial test=CBC w smear showing hemoltic anemia w bite cells and heniz bodies. Most accurate test is G6pD level a month after epidoe.
Most accurate test for PNH?
Absence of CD55/CD59 on flow cytometry. PNH is a normocytic anemia with intrinsic hemolysis (increased retics).
Warm AIHA and Cold AIHA. Acc’d Abs?
Warm: IgG, assc’d w SLE, CLL, drugs.
Cold: IgM, assc’d with mycoplasma and mono.
COLD MOM
warm Tx=steroids if severe
Cold=aboid cold and rituximab (anti CD20 Ab).
Hemoglobinuria predisposes to what renal issue?
ATN and renal failure
Symptoms for acute intermittent porphyria? 5 P’s
Painful abdomen Port-wine urine Polyneuropathy Psych disturbances Precipitated by drugs
best initial test: urine and plasma porphyrin levels
Aboid triggers and provide symptomatic treatment. High doses of glusocse decrease heme synthesis during attacks.
3 types of transfusion reactions? timing + mechanism+ tx?
Febrile nonhemolytic reaction: fever, chills, malaise 1-6 hours post-transfusion. Caused by cytokine formation during storage of blood. Stop transfusion and give tylenol
Allergic: Prominent urticaria caused by Ab formation against donor proteins. give antihistamines. If severe reaction, stop transfusion and give epi.
Hemolytic transfusion reaction: Fever, chills, nausea, flusing, buring at IV site, tachucardia, hypotension during or shortly after transfusion. Caused by preformed or formed Abs against donor srythrocytes due to ABO mismatch or RHD antigens. Stop transfusion and give fluids.
Elderly man w hypochromic, microcytic anemia is asx. labS?
FOBT and sigmoidoscopy, suspect CRC.
Most common inherited cause of hypercoagulability
Factor V leiden mutation
most common inherited bleeding disorder
VWD
Most common inherited hemolytic anemia + diagnostic test?
hereditary spherocytosis. osmotic fragility test.
What type of anemia causes pure RBC aplasia?
Diamond-Blackfan anemia
Anemia associated with absent radii and thumbs, diffuse hyperpigmentation, cafe-au-lait spots, microcephaly, and pancytopenia?
Fanconi anemia
Medications and viruses that lead to aplastic anemia.
Chloramphenicol, sulfonamides, radiation, HIV, chemo, hepatitis, parvo, EBV
How to distinguish primary vs. secondary polycythemia?
Both will have increaed HCT and RBC mass but primary /polycythemia vera will have a normal O2 sat and low EPO levels
HUS triad?
Anemia, Thrombocytopenia and acute renal failure
TTP tx?
Emergent plasmapheresis, steroids, antiplatelet drugs. PLT transfusion is contraindicated
ITP tx in kids
usually supportive care only. But if severe, steroids and IVIG
Which of the following are increased in DIC: fibrin split products, D-dimer, fibrinogen, platelets, and hematocrit?
Fibrin split products and D-dimer are elevated. Plts, fibrinogen and hematocrit are decreased.
A 9yo w hemarthrosis and PTT increased w/ nl PT and bleeding time. Dx? Tx?
Hemophilia A or B. Consider mixing study, consider sesmopressin for Hemo. A
14 yo w prolonged BT after dental procedure, nl PT, increased PTT. Dx? Tx?
vWD. tx w desmopressin, FFP or cryoprecipitate.
60 yo AA man w bone pain. work up for multiple myeloma might reveal?
lytic lesions in skull and long bones., serum protein analysis w M-spike, Benge Jones proteinuria
Reed sternberg cells present in what dz?
Hodgkin lymphoma
10 yo w b-cell cymptoms and anterior mediastinal mass. Dx?
NHL
80 yo man w fatigue, lymphadenopathy, spelnmegaly and isollated lymphocytosis. Suspected dx?
CLL
Pt w fatigue found to have increased MCV and decreased Hb. DDX?
folate, B12, alcohol,
late, life-threatening complication of CML
Blast crisis (fever, bone pain, splenomegaly, and pancytopenia)
Auer rods on blood smear
AML
AML sybtype associated w DIC?
M3. Tx w retinoic acid
Electrolyte changes in tumor lysis syndrome?
Hyper Phos, Hyper K, Hypoca, Hyperuricemia
50 yo w early satiety, splenomegaly, bleeding and t(9,22)?
CML
Pt w ANC of 1000 a fever? best next step?
broad-spectrum ABX
10 yo with Sickle cell dz presents w bone pain. Mangamenet?
O2, hydration, pain management, if severe, transfuse
Significant cause of morbidity in thalassemia patients?
Iron overload. Tx=deferoxamine
15 yo presents with WBC of 56,000 following dx of mono. MD orders a leukocyte alk phos to distinguish between a leukemoid reaction and malignancy. What do you expect?
The leukocyte alk phos (LAP) would be elevated in a mono patient. In contrast, LAP would be decreaesd in a pateient with a hematologic malignancy
Common lab finding in patients w CLL?
Lymphocytosis (increased NK, T or B ells)
Common lab finding in patients w CML
Increased granulocytes. (neutrophils, eosinophils, basophils)
40 yo w fatigue, hepatosplenomegaly, peripheral smear shows myeloblasts w kidney shaped nuclei and prominent nucleoli. Dx?
AML. Think MPO+ and Auer rods present. Fine granules in myeloblasts.
40 yo w weight loss and splenomegaly. CBC shows high WBC count. LDH, Urate, and B12 levels are high. Most accurate test? Dx?
CML. Most accurate test: t(9:22) cia PCR or FISH.
PDT for hairy cell leukemia
P: pancytopenia, splenomegaly, fatigue, petechiae, bruising, infection (esp. w MAC), abd. pain, early satiety
Best initial test: CBC w smear showing mononuclear cells w mnay cytoplasmic projections (hairy cells) that stain w TRAP (tartrate-resistant acid phosphatase.
T: cladribine, alternatives include splenectomy and IFN-alpha
NHL vs. HL. Nodal involvement of each? Cell line distinctions? Epi?
NHL has many peripheral nodes involved, can have extranodal and non-contiguous spread. HL involves a single group of localized nodes, spreads contiguously, rarely involves extranodal sites.
NHL comprised mainly of B-cells, rarely T.
HL has Ree-Sternberg cells (owl eyes). Distinct CD 15+ and CD30+ cells.
NHL peak incidence 65-75.
HL bimodal age distribution of old and young.
NHL assc’d w HIV and autoimmune conditions.
HL associated with EBV.
When are lymphnodes more likely to be benign?
Benign usually = from infection
Benign nodes are generally bilateral, <1cm, mobile, nontender in viral infxn and tender in bacterial infxn
PDT for Multiple Myeloma
P:
Mnemonic: MM=CRAB: hyperCalcemia, Renal involvement, Anemia, Bone pain (lytic lesions)
D: best initial test=SPEP showing IgG or IgA (resulting in M spike)
Most accurate test: bone bx showing > 10% monoclonal CD 138+ plasma cells.
Also CBC shows rouleax, urinalysis may show Bence Jones protein. Total protein:albumin gap is often elevated.
Tx: pts<70 can be tx w autologous bone marrow transplant
older than 0=melphalan (an oral alkylating agent) and prednisone
What is a monoclonal expansion of plasma cells that is asymptomatic and may eventually lead to multiple myeloma?
MGUS
What renal syndrome may result from multiple myeloma?
adult Fanconi syndrome can develop due to renal tubule damage
PDT for Waldenstrom Macroglobulinemia
P: malignant monoclonal gammopathy w eelevated IgM levels and hyperviscosity syndrome. Pts present w lethargy, weight loss, Rayaud, neuro problems including mental status changes, sensorimotor peripheral neuropathy and blurry vision (engorged blood vessels can be noted on eye exam). MGUS is a precusor.
Dx: one Bx and aspirate. Abnormal plasma cells w Dutcher Bodies (PAS+ IgM deposits around nucleus). SPEP, and UPEP can also be used. labs may also reveal: elevated ESR, urate, LDH and Alk Phos
T: Chemo for underlying malignancy
3 disorders that involve elevated IgM?
Cryoglobulinemia, Waldenstrom macroglobulinemia, and cold agglutinins. Note that cryoglobulinemia is most common in HCV and has systemic signs such as joint pain and renal involvement whereas cold agglutinins cause numbness upon cold exposure and are seen w EBV, mycoplasma infxn and Waldenstrom.
ANC cutoff?
<1500
Causes of secondary eosinophilia
NAACP: Neoplasm, Allergies, Asthma, Collagen vascular disease, Parasites
level for eosinophilia?
Absoloute eosinophil count>350/mm
Xeroderma pigmentosum. Associated Neoplasm?
squamous cell and basal cell carcinomas of the skin
Actinic keratosis
squamous cell carcinoma of skin
Multiple dysplastic nevi
malignant melanoma
Down syndrome
ALL
Immunodeficiencies
Malignant lymphomas
AIDS
NHL and KS
Autoimmune diseases (myasthenia gravis)
benign and malignant thymomas
chronic atrophic gastritis, pernicious anemia, postsurgical gastric remnants
gastric adenocarcinoma
Barret esophagus (chronic GI reflus)
esophageal adenocarcinoma
Plummer-Vinson syndrome (atrophic glossitis, esophageal webs, anemia, all due to iron deficiency)
squamous cell carcinoma of the esophagus
Acanthosis nigricans
visceral malignancy (stomach, lung, breast, uterus)
Tuperous sclerosis (facial angiofibroma, seizures, mental retartadation)
astrocytoma and cardia rhabdomyoma
Paget Disease of bone
secondary ostepsarcoma and fibrosarcoma
Pt w recent splenectomy surgery. now w increased plt count. dx?
Secondary (reactive) thrombocythemia. Spleen removes old plts and spleen is now gone. therefore elevated plts.
5 Ps of acute intermittent porphyria?
“five P’s” of acute intermittent porphyria: Painful abdomen, Polyneuropathy, Psychologic disturbances, Precipitated by drugs/alcohol, and Purple pee.
PDT for myelodysplastic syndrome
Epi: Hamatopoietic stem cell neoplasm
Risk increases with older age, previous chemotherapy
May transform to acute leukemia
P: Cytopenias (anemia, leukopenia, thrombocytpenia). HSM & lymphadenopathy
D: Dysplastic WBC+RB (ovalomacrocytosis and neutrophil hyposegmentation)
BMB (hypercellular marrow)
T: Transfusion for cytopenias
Chemo
hematopoietic stem cell transplant
