Hematology

Question 1

essential thrombocythemia

Answer 1

excessive, clonal platelet production and disease-related complications of thrombosis/hemorrhage, pregnancy loss
Inc with age
Hx: vasomotor manifestations (HA, lightheadedness, syncope, atypical CP, paresthesias, and transient visual disturbances)
PE: splenomegaly, livedo reticularis, erythromelalgia
Labs: inc platelets, +JAK 2, platelets vary in size on smear, LDH and uric acid WNL or slightly elevated, bone marrow bx: prominent large to giant megakaryocytes with abundant mature cytoplasm and deeply lobulated and hyperlobulated nuclei
Dx: 4 major OR 3 maj +1 minor
Major: Inc platelet count (>450K); characteristic bone marrow biopsy findings; presence of JAK2, CALR, or MPL mutation; and neg BCR-ABL1+ chronic myeloid leukemia, polycythemia vera, primary myelofibrosis, myelodysplastic syndromes, or other myeloid neoplasms.
Minor: presence of a clonal marker or absence of evidence for reactive thrombocytosis
Txt: cytoreductive or platelet-lowering therapy (hydroxyurea), anticoagulation (anagrelide), aspirin, or a combo

Question 2

Polycythemia vera

Answer 2

BCR-ABL1-negative myeloproliferative neoplasm
Inc red blood cell mass, bone marrow myeloproliferation, and mutation of JAK2
Hx: HA, dizziness, aquagenic prurtiis, facial plethora, erythromelalgia, engorged retinal veins, thrombosis, gouty arthritis
PE: HTN, splenomegaly
Dx: 3 maj OR 2 maj + 1 minor
Major: Hg >16, Hct> 38, red cell mass > 25% predicted, BM bx: hypercellularity with prominany erythroid, granulocytic and megakaryocitic proliferation with mature megakaryocytes, JAK 2 mutation
Minor: low EPO
Txt: phlebotomy PRN Hct < 45% to reduce thrombotic events and deaths from cardiovascular causes, hydroxyurea, ASA, JAK2 inhibitor (high-risk patients with sxs splenomegaly or severe constitutional sxs)

Question 3

Immune thrombocytopenia

Answer 3

thrombocytopenia caused by immunologic destruction of normal platelets, acute, after viral infxn
Hx: petechiae, gingival bleeding, epistaxis, menorrhagia, GI bleeding, intracranial bleeding
Txt: 20-30K without bleeding try corticosteroids, >30 with bleeding then IVIG, 2nd line: rituximab, Splenectomy and thrombopoietin receptor agonists.

Question 4

Primary hypotensive reaction during transfusion

Answer 4

diagnosis of exclusion characterized by a decrease in systolic, diastolic, or both systolic and diastolic blood pressures by at least 30 mm Hg within minutes of transfusion initiation. Ceasing transfusion results in the return of blood pressures to baseline

Question 5

Transfusion related acute lung injury (TRALI)

Answer 5

caused by Donor anti-leukocyte antibodies
fever, hypoxemia, new-onset acute respiratory distress syndrome within six hours of transfusion initiation
CXR: bilateral pulmonary infiltrates
If alternative risk factors for acute respiratory distress syndrome exist cannot be sure (e.g., pulmonary contusion, pneumonia, sepsis, pancreatitis)
Txt: immediate transfusion discontinuation. O2 supplementation with noninvasive methods or endotracheal intubation (needed in 80%), vasopressors and fluids for hypotension

Question 6

Anaphylactic transfusion reaction

Answer 6

IgG or IgE immune reaction elicits a sudden mast cell and basophil release of histamine, tryptase, and other mediators systemically within seconds to minutes after initiating a transfusion.
Sxs: hypotension, shock, respiratory distress, or angioedema. Flushing, urticaria, and pruritus
may occur in patients who are IgA deficient due to the development of class-specific IgG Ab to IgA
Txt: stop transfusion, epinephrine, intravenous fluids, airway maintenance, oxygenation, and vasopressors as needed

Question 7

Febrile transfusion reaction

Answer 7

Fevers, chills, malaise
Most common transfusion reaction
Txt: supportive care, Tylenol

Question 8

Hemolytic transfusion reaction

Answer 8

Immediate fevers, chills, HA, N/V, dark urine, hypotension
Most serious rxn, usually clerical error, ABO incompatibility
Txt: stop transfusion, vigorous crystalloid infusion, diuretic therapy to maintain UO

Question 9

Allergic reaction

Answer 9

Urticaria, hives
Ab mediated response to donor plasma
Txt: antihistamines

Question 10

Delayed transfusion reaction

Answer 10

Fall in Hg, drop in bilirubin
3-4 w after transfusion as primary response to RBC Ag
Txt: supportive care and stop transfusion

Question 11

Transfusion related graft vs host disease

Answer 11

Rash, elevated LFTs and pancytopenia
In immunocompromised patients, use irradiated!
Txt: stop transfusion and supportive care

Question 12

Autoimmune hemolytic anemia

Answer 12

IgG antibodies that react with protein antigens on red blood cells, also termed warm agglutinins, SLE patients
Can occur with viral infections, HIV, autoimmune disease, immune deficiency disease, malignancies, blood transfusion, organ transplantation, and drugs (Abx, NSAIDS)
Sxs: Hg 8-9: dyspnea, fatigue, bounding pulses, palpitations, and “roaring in the ears.” Hg<8: lethargic, confused, tachycardic, and dyspneic
PE: Pallor, jaundice, and splenomegaly, resting tachycardia, narrow pulse pressure, diaphoresis, pulmonary congestion, peripheral edema, and elevated jugular venous pressure
Labs: moderately to severely anemia, inc reticulocyte count, indirect bilirubin, and LDH, low serum haptoglobin, + direct antiglobulin (Coombs), spherocytes on peripheral smear
Txt: treat underlying cause, steroids, immunosuppresion, splenectomy

Question 13

Microangiopathic hemolytic anemia

Answer 13

nonimmune hemolytic anemia 2/2 endothelial shearing and damage of RBC
Caused by malignant HTN, TTP, HUS, DIC, vasculitis, eclampsia, and metastatic cancer
Labs: schistocytes on peripheral smear, Inc LDH, indirect bilirubin, and low haptoglobin
Txt: treat underlying disorder

Question 14

Antiphospholipid antibody syndrome,

Answer 14

arterial and venous thrombosis and the presence of anti-beta-2-glycoprotein I Ab, anticardiolipin Ab, or lupus anticoagulant, associated with SLE
Sxs: miscarriages in pregnancy, DVT, thrombocytopenia, livedo reticularis, stroke, superficial thrombophlebitis, PE, TIA
Txt: low-dose aspirin and prophylactic-dose LMWH to prevent pregnancy complications

Question 15

Factor V Leiden mutation

Answer 15

family history, patients with initial unprovoked venous thrombosis (particularly those occurring at age < 50), recurrent thromboembolisms, or thromboembolisms affecting unusual vascular beds
Dx: genetic testing for the factor V Leiden mutation or by a second-generation activated protein C resistance assay>if positive then confirm if homo/heterozygous for gene mutation

Question 16

Alpha thalesemmia

Answer 16

> 1 of 4 alpha globin chains genes defect
1 deletion-asx carrier
2 deletions=minor: asx with mild microcytic anemia
3 deletions= HgH diseasae: splenomegaly, hemolytic and microcytic anemia, avoid oxidative drugs
4 deletions=hydrops fetalis, fetal demise, total body edema

Question 17

Von Willebrand’s disease

Answer 17

autosomal dominant pattern of inheritance, reduced levels of functioning von Willebrand factor
Sxs: bruising and epistaxis, hematomas, menorrhagia, and bleeding from minor wounds, surgeries, or dental extractions
Labs: low Factor VIII level
Txt: desmopressin (DDAVP)

Question 18

acute intermittent porphyria

Answer 18

partial deficiency in porphobilinogen deaminase
women of reproductive age and may be associated with caloric deprivation during an illness, fast, or after bariatric surgery
Sxs: fatigue, poor concentration, abdominal pain and weakness, nausea, vomiting, and neurological signs (weakness, dysesthesia, and an altered affect), red urine
Labs: low Na/Mg, high Ca, elevated LFTs
Dx: porphobilinogen level 10–150 x the ULN in urine or plasma
Txt: review meds (phenytoin, barbituates), IVF, the use of antiemetic agents and analgesic agents, and if required the use of antiepileptic medications. Acute attack> IV heme.

Question 19

Beta thaleseemia

Answer 19

mutation in the beta-globin gene that leads to decreased beta-globin synthesis
Mediterranean, Asian, African
single beta-thalassemia allele: beta-thalassemia minor: asx, mild microcytic anemia. increased Hg A2 (comprised of two alpha and two delta chains)
No alleles: Beta-thalassemia major: complete absence of Hg A, severely anemic and require lifelong transfusions or a bone marrow transplant, “crew cut” skull x-ray, “chipmunk” facies

Question 20

primary (clonal) hypereosinophilic syndrome

Answer 20

Caused by allergies, infection, rheumatologic conditions, and malignancy
Sxs: CHF, thromboembolism, and neurologic abnormalities.
Labs: peripheral blood eosinophilia >1500
Dx: FIP1L1-PDGFRA gene fusion protein that can transform hematopoietic cells
Txt: tyrosine kinase inhibitor imatinib

Question 21

HIT (Heparin-induced thrombocytopenia)

Answer 21

IgG Ab that form a complex with platelet factor 4, a chemokine that binds to heparin, and subsequent activation of platelets causing thrombosis
Dx: 5 days after initiation of heparin, decrease in platelet count by 50% and evidence of thrombosis
Txt: DC heparin, direct thrombin inhibitor (argatroban) and the factor Xa inhibitor danaparoid, can use LMWH fondaparinux and the direct thrombin inhibitor bivalirudin
Type 1: PLT recovery with or without heparin cessation
Type 2: autoimmune, venous/arterial thromboses

Question 22

Sideroblastic anemia

Answer 22

> 65 years, hx of prolonged exposure to toxins (ethanol, lead, or isoniazid), x-linked recessive, mitochondrial defect that prevents the incorporation of iron into hemoglobin
Labs: mild anemia, inc Fe and ferritin. TIBC normal or dec, transferrin dec, Reticulocyte count low, smear dimorphic cell population, Bone marrow ringed sideroblasts when stained with Prussian blue

Question 23

Lead poisoning

Answer 23

construction, mining, welding, moonshine exposure, children-lead paint
Sxs: HA, joint pain, and constipation, nausea, vomiting, ataxia, encephalopathy, seizure
Imaging: XR hyperdense lines at metaphyses (“lead lines”)
Labs: normocytic, hypochromic anemia, and basophilic stippling on peripheral smear
Txt: PO succimer or IV EDTA (calcium disodium edetate, given after dimercaprol)

Question 24

Benign ethnic neutropenia

Answer 24

absolute neutrophil count < 1,500 but >1200
common inherited condition in African descent, West Indians, Yemenites, Sephardic Jews, Greeks, and Arabs.
Do not have an increased risk of infection.

Question 25

Antithrombin deficiency

Answer 25

autosomal dominant inheritance or caused by DIC, acute thrombosis, liver disease, nephrotic syndrome, ECMO, and use of heparin
Sxs: elevated risk of thrombosis (venous), heparin resistance (inability to reach the desired activated PTT)
Dx: functional assay for plasma antithrombin activity> Enzyme-linked immunosorbent assay for antithrombin protein level, testing should not occur during acute thrombosis, genetic testing for antithrombin deficiency may be diagnostic
Txt: Asx-none, Prophylactic anticoagulation in pregnancy and 6 weeks postpartum and perioperatively if hx of VTE or in first-degree relatives

Question 26

post-transfusion purpura

Answer 26

purpura approximately 6 days after transfusion due to development of anti-human platelet antigen (HPA)-1a Ab, multiparous women
Sxs: acute decrease in platelet count, purpura
Dx: thrombocytopenia and purpura and confirmed by the presence of anti-human platelet antigen (HPA)-1a antibodies
Txt: IVIG. Plasmapheresis and corticosteroids may be used in treatment as well.

Question 27

Thrombotic Thrombocytopenic Purpura (TTP)

Answer 27

Woman, severely decreased protease ADAMTS13 activity
Sxs: fever, confusion, difficulty speaking, headache, seizure, nausea, vomiting, diarrhea
Labs: inc LDH, elevated indirect bilirubin, normal coagulation studies, microangiopathic hemolytic anemia, and thrombocytopenia
Txt: plasma exchange with IV corticosteroids

Question 28

aplastic anemia

Answer 28

bone marrow failure with a high mortality rate associated with a loss of hematopoietic stem cells
due to autoimmunity, drugs (chloramphenicol, and antiepileptic (carbamazepine, phenytoin), nifedipine, Azathioprine-induced in SLE), chemicals, irradiation, viral infection, and clonal or genetic disorders
Sxs: recurrent infections, mucosal, fatigue
Labs: pancytopenia
Dx: Bone marrow biopsy-hypocellularity, increased fat cell deposition in bone marrow stroma, a lack of dysplastic cells, and a lack of fibrosis or infiltration with malignant cells
Severe aplastic anemia: ANC< 500, < 20,000 platelets, and reticulocyte <20,000
Txt: severe disease-hematopoietic cell transplantation or immunosuppressive therapy with eltrombopag.

Question 29

Glucose-6-phosphate dehydrogenase deficiency (G6PD)

Answer 29

does not allow cells to regulate oxidative stress
X-linked recessive disorder
Sxs: asx, in cases of oxidative stress, such as infection, medications (antimalarial like hydroxychloroquine, sulfonamides, nitrofurantoin), or certain foods (fava beans)> hemolytic anemia
Labs: Heinz bodies on smear, bite cells