Lymphoma-and-CLL Flashcards
ABVD
doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is standard;
Rx: Hodgkin’s Stage I and II
- Stages I and II: ABVD followed by radiation. - Some cases may be treated with chemotherapy alone. - Stages III and IV: full-course ABVD followed by Radiation may be added afterward to areas of bulky tumor. Combination therapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is standard; full-course is six to eight cycles
Complication of Anthracyclines
Late cardiomyopathy
CML vs AML
- AML: acute onset
- AML: blast cells
- CML: splenomegaly
Anemia: Iron deficiency:
why is it common in dialysis patients?
Blood loss during procedures and labs
AL amyloidosis vs AA amyloidosis
- AL amyloidosis: monoclonal gammopathy caused
- AA amyloidosis: chronic inflammatory conditions such as RA or Hodgkin’s
Amyloidosis is a generic term that refers to the extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of proteins, many of which circulate as constituents of plasma. These subunit proteins are derived, in turn, from soluble precursors which undergo conformational changes that lead to the adoption of a predominantly antiparallel beta-pleated sheet configuration. At least 30 different human protein precursors of amyloid fibrils are known (table 1). (See ‘Pathogenesis’ above.)
●The two major forms of amyloidosis are the AL (primary) and AA (secondary) types. AL amyloid, the most common form in developed countries, is due to deposition of protein derived from immunoglobulin light chain fragments. It is a plasma cell dyscrasia in which a monoclonal immunoglobulin is detectable in the serum and/or monoclonal light chains in the urine in approximately 80 percent of cases. (See ‘AL amyloidosis’ above and ‘Clinical manifestations’ above.)
AA amyloidosis, the most common form in developing countries, may complicate chronic diseases in which there is ongoing or recurring inflammation, such as chronic infections; rheumatoid arthritis (RA), spondyloarthropathy, or inflammatory bowel disease; or periodic fever syndromes.
Vitamin K dependent clotting factors
II, VII, IX, X
Hemophilia A: The INR is _
normal
measures the time it takes plasma to clot when exposed to tissue factor, which assesses the extrinsic and common pathways of coagulation
PT
Common causes of a prolonged PT include anticoagulants, vitamin K deficiency, liver disease, and disseminated intravascular coagulation (DIC). Some coagulation factor deficiencies may also prolong the PT (table 1).
The international normalized ratio (INR) was developed to allow patients receiving warfarin at steady state to compare values obtained at different times and from different laboratories; it is also commonly used as a surrogate for the PT in bleeding patients and to assess end-stage liver disease as part of the model for end-stage liver diseases (MELD) score. (
Coagulation tests: measures the time it takes plasma to clot when exposed to substances that activate the contact factors coagulation, which assesses the intrinsic and common pathways of coagulation.
aPTT
The activated partial thromboplastin time (aPTT) measures the time it takes plasma to clot when exposed to substances that activate the contact factors coagulation, which assesses the intrinsic and common pathways of coagulation.
Causes of a prolonged aPTT include anticoagulants; liver disease; DIC; von Willebrand disease (VWD); inherited deficiency of factor VIII (hemophilia A), factor IX (hemophilia B), factor XI, or other coagulation factors; acquired factor inhibitors; and antiphospholipid (aPL) antibodies. (See ‘Activated partial thromboplastin time (aPTT)’ above.)
ESLD: bleeding + low fibrinogen: Rx
Cryoprecipitate
Why not FFP? Cryoprecipitate is rich in fibrinogen
Bleeding: Renal failure: Immediate Rx
Meta: ImmediateRx
Desmopressin
Uremia causes platelet dysfunction: desmopressin rapidly/transiently increasing Factor VIII (decreasing aPTT) and VWF factor (decreasing BT).
Low platelets 1 hour after transfusion:
Check HLA compatibility
Bleeding: mixing studies indications
Mixing studies are appropriate in a patient with an unexplained prolongation of a clotting test; they distinguish between an abnormally prolonged clotting time due to a factor deficiency versus a factor inhibitor (typically, an autoantibody).
VWF disease: how can it lead to Factor VIII deficiency?
VWF deficiency leads to increased clearance of Factor VIII
Factor VIII inhibitor: actively bleeding patient:
Rationale for giving Factor VIIa
It bypasses the Factor VIII inhibitor
Bleeding: how are acquired antibodies to coagulation factors detected?
Acquired antibodies to the clotting factors are often diagnosed by mixing studies, in which addition of patient plasma to normal plasma causes the relevant clotting test to become abnormal due to the antibody.
For patients with a low titer factor VIII inhibitor (eg, <5 Bethesda units) and active bleeding, we suggest initial control of active bleeding using a human factor VIII product (recombinant factor VIII or a factor VIII concentrate) rather than another product (Grade 2C). A typical dose is 20 international units/kg intravenously for each Bethesda unit of the inhibitor, plus an additional 40 international units/kg, with monitoring of factor VIII activity 10 minutes following bolus injection, and repeat intravenous bolus dosing if the incremental recovery is not adequate.
Bleeding: Factor VIIIa inhibitor: Rx
Comment: Never seen a case
- low titer: factor VIII
- high titer: Factor VIIa
- Prednisone
For patients with a low titer factor VIII inhibitor (eg, <5 Bethesda units) and active bleeding, we suggest initial control of active bleeding using a human factor VIII product (recombinant factor VIII or a factor VIII concentrate) rather than another product (Grade 2C). A typical dose is 20 international units/kg intravenously for each Bethesda unit of the inhibitor, plus an additional 40 international units/kg, with monitoring of factor VIII activity 10 minutes following bolus injection, and repeat intravenous bolus dosing if the incremental recovery is not adequate. (See ‘Control of active bleeding’ above.)
●For patients with a high titer factor VIII inhibitor (eg, ≥5 Bethesda units) and active bleeding, we suggest using an activated prothrombin complex concentrate (aPCC; eg, factor VIII inhibitor bypassing activity [FEIBA]) or recombinant human factor VIIa (rfVIIa) rather than a human factor VIII product (Grade 2C). Human factor VIII generally cannot be given in high enough amounts to overcome the inhibitor. Recombinant porcine factor VIIIa is also an option. The choice of product depends on availability, initial or previous responses, and clinician preference. (See ‘Control of active bleeding’ above.)
●To eliminate factor VIII inhibitors we recommend the use of prednisone at an initial oral dose of 1 mg/kg per day in all patients (Grade 1B). Based upon weak evidence from the literature and our own experience, we suggest that oral cyclophosphamide (2 mg/kg per day) be added to the initial prednisone treatment regimen (Grade 2C). (See ‘Eliminating the inhibitor’ above.)
●Inhibitors of prothrombin are frequently associated with antiphospholipid antibodies. Treatment of active bleeding is done with fresh frozen plasma (FFP). Modalities associated with factor VIII antibodies may also be useful. (See ‘Prothrombin (factor II) inhibitors’ above and ‘Treatment of factor VIII inhibitors’ above.)
PBS: polychromasia: Implies
Meta: implies, signifies
Indicating an increase in young RBCs
RBC Description terms
- Anisocytosis: Differently sized RBCs
- Poikilocytosis: Differently shaped RBCs
- Polychromasia: Indicating an increase in young RBCs
- Microcytosis: Small RBCs
- Macrocytosis: Large RBCs
- Schistocytes: Fragmented RBC forms
PBS: RBC forms
A, Schistocytes. B, Macrocytes. C, Spherocytes. D, Teardrops, bizarre shapes.
Hypochromic, microcytic: Ddx
Iron deficiency
Thalassemia
Anemia of chronic disease
PBS: describe and Dx
Burr cell
Uremia
PBS: describe and dx
Acanthocyte
Liver disease
Abetalipoproteinemia
Echinocytes — Echinocytes (burr cells) are red cells with serrated edges over the entire surface of the cell, and often appear crenated in a blood smear (picture 3). The projections of the red cell membrane are smaller and much more uniform in shape and distribution in echinocytes than in acanthocytes.
Acanthocytes — Acanthocytes have only a few spicules of varying size that project from the red cell surface at irregular intervals (picture 4). Spur cells appear to be the extreme form of acanthocytes and are seen in patients with severe liver disease.
Causes
●Echinocytes are often found as artifacts on blood smears and have been demonstrated in both end-stage renal disease and in liver disease.
●Patients with liver disease often have acanthocytes, echinocytes, and target cells on the peripheral blood smear. Spur cells are the extreme form of acanthocytes. They are probably acanthocytes that have been additionally remodeled by an enlarged spleen and considerably enriched in cholesterol. (See ‘Pathophysiology’ above.)
PBS: schistiocyte: DDx
Microangiopathic hemolytic anemia (e.g., TTP, DIC)
Malignant hypertension
Prosthetic heart valve
PBS: spherocytes: Ddx
Autoimmune hemolytic anemia
Hereditary spherocytosis
Macrocytes: Ddx
Vitamin B12 deficiency
Folate deficiency
Myelodysplastic syndrome
Liver disease
Hypothyroidism
PBS: Teardrops, nucleated RBCs, bizarre forms: Ddx
Myelofibrosis Marrow infiltration (e.g., tumor, tuberculosis)
PBS: Bite cells: Ddx
G6PD, unstable hemoglobinopathy
PBS: Leukopenia with hyposegmented PMNs
Myelodysplastic syndrome
Stress, infection
Pelger-Huët anomalyBone marrow examination with cytogenetics/FISH if myelodysplastic syndrome suspected
PBS: Roueleaux
Myeloma
PBS: arrow is pointing at
Blood smear from a patient with B cell chronic lymphocytic leukemia. The predominant lymphocytes have a very sparse cytoplasm, round to slightly oval nuclei, and no evident nucleoli. Damaged lymphocytes (“smudge cells”) are present (arrows).
Leukopenia with hypersegmented PMNs
B12 deficiency, folate deficiency
PBS: Lymphocytosis with normal-appearing lymphocytes
CLL
PBS: Lymphocytosis with open nuclei/nucleoli
Activated lymphocytes (e.g., seen in viral infection)Clinical correlation and viral serologies as appropriate; flow cytometry to rule out leukemia/lymphoma
PBS: Leukocytosis with wide range of immature forms
Reactive bone marrow (i.e., leukemoid reaction)
Chronic myelogenous leukemia
Myeloproliferative neoplasm
PBS: Immature cells
Myeloblasts with Auer rod in acute myeloid leukemia
Peripheral smear from a patient with acute myeloid leukemia. There are two myeloblasts, which are large cells with high nuclear-to-cytoplasmic ratio and nucleoli. Each myeloblast has a pink/red rod-like structure (Auer rod) in the cytoplasm (arrows).
PBS: RBCs should be round and the size of a _ nucleus, with one-_ central pallor
RBCs should be round and the size of a lymphocyte nucleus, with one-third central pallor
PBS: Polymorphonuclear neutrophils (PMNs) should have _ to four lobes
Polymorphonuclear neutrophils (PMNs) should have three to four lobes
Flow cytometry
Flow cytometry: Quantitates cell surface markers and can also establish clonality
A sensitive method of determining specific cytogenetic abnormalities. It does not require proliferating cells and can thus be performed on peripheral blood, but limited to specific probes for known abnormalities.
FISH
PCR: limitations
Polymerase chain reaction (PCR): A highly sensitive method for looking at mutations; can be qualitative or quantitative, but limited to known mutations for which there are primers
Bone marrow: components
A bone marrow examination consists of two components: (1) a bone marrow aspirate and (2) a bone marrow biopsy
Ctyogenetics vs FISH/PCR
Cytogenetic analysis requires dividing cells, which are usually found only in the marrow (as opposed to peripheral blood); it is less sensitive than FISH or PCR but not limited by specific probes.
Bone marrow: low yield for
Bone marrow aspirate has a relatively low yield for evaluation of fever of unknown origin or aggressive lymphoma (excisional biopsy of an affected lymph node is preferred)
Bone marrow biopsy
The bone marrow biopsy is a core biopsy that is then decalcified
most helpful in determining cellularity
Bone marrow:
An 85-year-old woman presents with mild pancytopenia and macrocytosis. The remainder of her physical exam and laboratory data are normal. On bone marrow biopsy her cellularity is 50%.
MDS
The typical normal cellularity of bone marrow can be determined as 100 minus the age of the patient. Thus, this 85-year-old woman should have a cellularity of approximately 15%. A hypercellular bone marrow, macrocytosis, and pancytopenia are consistent with myelodysplastic syndrome.
Young female with no h/o bleeding or bruising presents with:
Menorrhagia
Epistaxis
Normal CBC
↑ Bleeding time and PTT; normal PT
↓ Factor 8 level
What is the diagnosis?
von Willebrand disease (vWD).
Explanation
Remember the difference in the presentation of von Willebrand disease (mucosal bleeding) compared with clotting factor deficiencies (joint and soft tissue bleeds), except in severe vWB disease, which can mimic a factor deficiency. This is a very complex illness, divided into 3 types with 4 subtypes. Even hematologists have a difficult time interpreting the laboratory results. Know how the disease presents and what screening tests to order.
Dx: Clinical suspicion + Factor 8 (low) + vWF:Ag (total vWF protein; decreased) + vWF:RCoF
(ristocetin-induced agglutination of normal platelets; decreased) + RIPA (ristocetin-induced agglutination
of patient’s platelets; decreased).
Tx: Depends on the form of vWD; mainstay is desmopressin (DDAVP®).
Rx: PCV
Tx: Phlebotomy to keep Hct < 45% ± myelosuppression (hydroxyurea) + aspirin for vasomotor symptoms.
Dx: There is no diagnostic consensus, but most patients have increased red cell mass + normal pO2 + exclusion of CML, ET, and myelofibrosis + hypercellular marrow with increased megakaryocytes.
Tx: Phlebotomy to keep Hct < 45% ± myelosuppression (hydroxyurea) + aspirin for vasomotor symptoms.
Patient on chronic iron supplementation for years because of a microcytic anemia presents with:
New-onset diabetes
Normal WBC and platelets
Mildly ↓ Hgb with MCV < 65 fL
Normal reticulocyte count and hemoglobin electrophoresis
Normal serum Fe, ↑ Fe/TIBC, ↑ ferritin
What
alpha thalassemia trait.
Explanation
The chronic mild anemia and low MCV is concerning for iron deficiency, yet iron studies do not reveal iron deficiency. Thalassemias cause mild anemias with a low MCV and are often misdiagnosed as iron deficiency. A normal Hgb electrophoresis in the setting of a microcytic anemia and the exclusion of iron deficiency allows you to diagnose α-thalassemia. Giving the patients iron long-term results in an iron overload state. It is difficult to diagnose hemochromatosis in someone who takes exogenous iron.
Dx: Clinical + diagnosis of thalassemia + normal iron studies + increased ferritin.
Tx: Discontinue iron supplements.
Bone marrow:
A 75-year-old man undergoing routine screening is found to have an immunoglobulin G (IgG) kappa monoclonal gammopathy of 1.2 g/dL. His physical examination is unremarkable. His complete blood count (CBC), serum free light chain assay, urinalysis, and kidney function are normal; skeletal survey is negative; and the remainder of his physical exam is normal. Dx/Mx:
MGUS, review in 6 months
The normal labs and exam in this man suggest that he has a monoclonal gammopathy of undetermined significance, with a rate of progression to myeloma of approximately 1% per year. A high percentage of elderly people have a monoclonal gammopathy, and it is not necessary, prudent, or efficient to evaluate all such people with a bone marrow examination.
Patients with an M-spike greater than 1.5 g/dL, a non-IgG monoclonal gammopathy, an abnormal free light chain ratio, or evidence of end-organ damage warrant a bone marrow examination.
Hereditary spherocytosis: Mx
Splenectomy
Hereditary spherocytosis: Rx
Dx: Clinical (including FH of hemolytic anemia) + spherocytes on peripheral smear + osmotic fragility test (abnormal).
Tx: Folate + iron and folic acid, perhaps supportive blood transfusions, and possibly splenectomy (total or partial).
Patient who has received previous transfusions receives another transfusion of packed red cells. 1 week later, he develops:
Fever and shortness of breath
↓ Hgb and Hct
↑ T. bili and I. bili
What is the diagnosis?
delayed hemolytic transfusion reaction.
Explanation
Note the presence of hemolysis, as reflected by the increase in the I. bili, but the event occurred 1 week after transfusion. This phenomenon is usually due to Rh incompatibility or minor antigen mismatches that result in the formation of low levels of antibodies after the original transfusion (such a low level that the cross-matching process does not pick them up). Anamnestic production of antibody occurs with subsequent transfusion. Most cases do not result in symptomatic hemolysis; this presentation is an extreme case.
Dx: Clinical + evidence of hemolysis (increased LDH and indirect hyperbilirubinemia + low haptoglobin
and positive Coombs test) + blood bank evaluation of pre- and post-transfusion samples with repeat
cross-matching.
Tx: Usually supportive care is adequate.
Fever and chills during a transfusion of packed red cells
Normal LDH, T. bili, and I. bili
Negative Coombs test
Normal haptoglobin
Negative urine free hemoglobin
What is the diagnosis?
Show Answer
Diagnosis is febrile nonhemolytic transfusion reaction.
Explanation
This is not an acute hemolytic transfusion reaction because the lab tests do not indicate hemolysis.
Dx: Clinical; exclude other causes of fever and exclude hemolysis.
Tx: Antipyretic ± meperidine for rigors
Patient ≥ 70 years of age presents with:
Painless cervical lymphadenopathy x weeks
Wheals at sites of mosquito bites
Splenomegaly
↑ WBC (Differential: ↑ Lymphocytes) ± ↓ Hgb, Hct, and Plt
Peripheral smear: Smudge cells
Positive Coombs test (if anemic)
What is the diagnosis?
Diagnosis is B-cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
Explanation
This disease can present as a chronic leukemia or as an indolent lymphoma. B-cell CLL has a bimodal age distribution: ≥ 70 years and between 30 and 39 years. Autoimmune hemolytic anemia and thrombocytopenia often occur. Most patients do not have the exaggerated response to mosquito bites, but this is 1 diagnosis to consider when you see such a response.
Dx: Monoclonal B-cell lymphocytosis (CD5+) or expansion of the marrow with the same cells.
Tx: Observation in early stage ± localized radiation therapy ± treatment options that include single-agent therapy with and combinations of chlorambucil, fludarabine, bendamustine, pentostatin and rituximab.
Healthy patient undergoes pre-op assessment for elective surgery.
No h/o bleeding or bruising
No h/o heparin exposures
Normal CBC
Normal PT
Prolonged PTT that corrects with 1:1 mix with normal plasma
Normal bleeding time
What is the cause of the coagulopathy?
rolonged PTT is Factor 12 deficiency.
Explanation
Suspect Factor 12 deficiency when you see a prolonged PTT without any history or clinical evidence of bleeding. It is not associated with a clinical bleeding disorder. The correction with the 1:1 mix tells you that an inhibitor is not the cause (an inhibitor would not correct with the mix).
Dx: Clinical + PT/PTT + 1:1 mix with normal plasma (corrects).
Tx: No treatment indicated.
Patient ≥ 60 years of age presents with:
Severe fatigue
Abdominal pain and/or fullness
Massive splenomegaly
↓ Hgb and Hct
↑ or ↓ WBC and Plt
Peripheral smear: Anisocytosis, poikilocytosis, and teardrops; large platelets and fragmented megakaryocytes
± Positive Coombs test
Marrow biopsy: “Dry tap”
What is the diagnosis?
primary myelofibrosis (MF).
Explanation
While myeloproliferative disorders can have splenomegaly (e.g., polycythemia vera [PV] and essential thrombocytosis [ET]), think about myelofibrosis (splenomegaly present in ∼ 90% of patients) when a case describes massive splenic enlargement. Hepatomegaly is also seen in ∼ 50% of patients. Marrow biopsies are difficult (resulting in a “dry tap”) because of the fibrosis, but some patients in early stages have hypercellular marrows with scant fibrosis. Buzzwords for this presentation are as follows: massive splenomegaly, teardrops, and dry tap.
Dx: Clinical + exclude other myeloproliferative disorders.
Tx: Transfusion support.
Young patient presents with:
Community-acquired pneumonia
Scleral icterus
↓ Hgb and RBC clumping
↑ Reticulocyte count
Slight ↑ indirect bilirubin and LDH, ↓ haptoglobin
Positive Coombs test
Cold agglutinins > 1:64
What is the cause of the anemia? What is it due to?
autoimmune hemolysis due to Mycoplasma infection.
Explanation
Remember the classic association between cold autoimmune hemolytic anemia (AIHA) and Mycoplasma and EBV infections.
Dx of autoimmune hemolysis: Clinical + Hgb (low) + evidence of hemolysis (increased indirect hyperbilirubinemia, reticulocyte count, and LDH; decreased haptoglobin) + positive Coombs test (C3 type = complement Coombs test).
Tx: Supportive (+ treat underlying Mycoplasma infection).
Adolescent patient presents with:
Recurrent epistaxis, menorrhagia, gum bleeding, and subjective excessive bleeding for minor cuts
FH of same
No NSAID use
Normal Hgb, ↓ platelets
Normal PT and PTT
Prolonged bleeding time
Normal Factor 8 levels
Peripheral smear: Giant platelets
What is the diagnosis?
Bernard-Soulier syndrome.
Explanation
Thrombocytopenia, giant platelets on the smear, and the prolonged bleeding time are the clues to Bernard-Soulier, a.k.a. giant platelet syndrome. The defect is absence of the GP1b-9-5 receptor. This is not von Willebrand’s because the labs are not right for that diagnosis (Factor 8 is often low and bleeding time is prolonged, and no giant platelets are seen).
Dx: Rare syndrome that is difficult to distinguish among other congenital platelet disorders (gray platelet syndrome, May-Hegglin anomaly, and some types of vWD); diagnosis is within the realm of the hematologic subspecialist.
Tx: Platelet transfusions prn.
dult patient with SC sickle cell anemia presents with:
Fever
Abdominal pain
Massive, tender splenomegaly
↓ Hgb
↑ Reticulocyte count
What is the diagnosis?
Diagnosis is acute splenic sequestration.
Explanation
Note that patients with SS sickle cell anemia autoinfarct their spleens in infancy, so they are not at risk for this presentation as adults. Patients with the milder SC disease, however, are at risk.
Dx: Clinical + reticulocytosis.
Tx: Red cell transfusion with splenectomy as a last resort.
Patient is readmitted to the hospital with:
Deep venous thrombosis after a recent brief hospital stay that included the prescription of heparin
Normal platelet count
What is the diagnosis?
heparin-induced thrombocytopenia (HIT).
Explanation
Clinical scenario could present an in-house patient who develops thrombocytopenia while on heparin. Highest risk of clots, however, is after the thrombocytopenia resolves, usually after the heparin has been discontinued. Recognize that platelets can be in the normal range if the patient had a thrombocytosis at the initiation of heparin.
Dx: Clinical (prediction models, such as the 4 Ts, are helpful) ± serotonin release assay (positive) or solid phase immunoassay (negative test excludes).
Tx: Stop heparins + lepirudin (do not use in patients with low GFR), argatroban, or fondaparinux
+ warfarin (after platelets rise to > 150,000) and overlap with alternative anticoagulation x 5 days.
During a transfusion of packed red cells, the patient develops:
Fever and chills
↑ LDH and indirect bilirubin
↓ Haptoglobin
Positive Coombs test
What is the diagnosis? What is the most likely cause?
acute hemolytic transfusion reaction. The most likely cause is ABO incompatibility.
Explanation
Anytime a patient has fever during a transfusion, consider this first.
Dx: Clinical + evidence of hemolysis (increased LDH and indirect hyperbilirubinemia + low haptoglobin
and positive Coombs test) + blood bank evaluation of pre- and post-transfusion samples with repeat
cross-matching.
Tx: Stop transfusion immediately + IVF support + furosemide-induced diuresis + monitoring for DIC (check PT/PTT, fibrinogen, fibrin degradation products, and D-dimer).
Female patient in her 70s presents with no complaints for annual evaluation with:
Pallor
↓ Hgb and Hct
± ↓ WBC, ↑ platelets, normal or ↑ MCV
↓ Reticulocyte count
Peripheral smear: Pseudo Pelger-Huet cells
Normal serum Na, K, Cl, HCO3, glucose, creatinine, AST, and ALT
Bone marrow: Hypocellular
Cytogenetics: 5q deletion
What is the diagnosis?
5q myelodysplasia.
Explanation
This subset of myelodysplasia is worth remembering because most patients are women and have a favorable prognosis. The 5q is a big clue, as is the thrombocytosis (not thrombocytopenia, as in most cases of myelodysplasia). These patients often respond favorably to lenalidomide and have increased survival compared with other myelodysplasias. Pseudo-Pelger—Huet cells (buzzwords to remember!) are seen in myelodysplastic states in which the granulocytes have decreased segmentation.
Dx: Anemia + preserved or increased platelets + lack of blasts + marrow cells with 5q31 deletion.
Tx: Lenalidomide.
haracterized by a white blood cell type known as a neutrophil whose nucleus is hyposegmented.[citation needed]
Pelger–Huët anomaly has an autosomal dominant pattern of inheritance.
Anomalies resembling Pelger–Huët anomaly that are acquired rather than congenital have been described as pseudo Pelger–Huët anomaly. These can develop in the course of acute myelogenous leukemia or chronic myelogenous leukemia and in myelodysplastic syndrome. It
Pseudo-Pelger—Huet cells
Patient with atrial fibrillation on warfarin is given piperacillin/tazobactam for 10 days to treat ascending cholangitis.
The normal dose of warfarin is given, but the patient’s INR increases.
What is the most likely cause of the increase in INR?
loss of vitamin K-producing organisms in the gut due to use of broad-spectrum antimicrobials.
Explanation
Certain cephalosporins can also do this when their side chain antagonizes vitamin K.
Dx: Clinical.
Tx: Stop the offending antimicrobial.
Patient ≥ 50 years of age presents with:
↓ Hgb and Hct, normal MCV and MCHC
↑ WBC (Differential: Myelocytes, metamyelocytes, segmented neutrophils, basophils, eosinophils, < 2% blasts)
↑ Plt
↓ Leukocyte alkaline phosphatase (LAP) score
Marrow biopsy: Hypercellular with granulocytic hyperplasia, < 20% blasts
Cytogenetics: t(9;22)(q32;q11.2)
What is the diagnosis?
chronic myelogenous leukemia (CML).
Explanation
The major clue here is the presence of the Philadelphia chromosome, the BCR-ABL translocation [t(9;22)], and the excess of granulocytes in various stages of development. Although it has poor sensitivity and specificity, the low LAP score may help you distinguish CML from a leukemoid reaction and polycythemia vera, both of which have increased LAP scores. If you see the same sort of presentation with low platelets, think more of myelodysplasia, not myeloproliferative disease. Remember: This is not acute leukemia because the peripheral blood contains a spectrum of differentiated granulocytes, and acute leukemia is marked by maturation arrest and overproduction of blasts. Acute leukemia is defined by > 20% blasts in the marrow.
Dx: Leukocytosis with excess myeloid cells + evidence of Philadelphia chromosome (the chromosome itself, evidence of the BCR-ABL fusion gene, or evidence of the BCR-ABL mRNA).
Tx: Based on phase and patient’s age; chronic and early accelerated phase is treated with a tyrosine kinase inhibitor; e.g., imatinib. Refractory and nonresponsive patients are treated with stem cell transplant.
Postpartum woman presents with:
Confusion, headache, fever, ± seizures
↓ Hgb and Plt
↑ Serum creatinine
↑ T. bili and indirect bilirubin , ↑ LDH, ↓ haptoglobin
Peripheral smear: Schistocytes
Negative Coombs test
Normal U/A
Normal PT and PTT
What is the diagnosis?
thrombotic thrombocytopenic purpura (TTP).
Explanation
This diagnosis is caused by ADAMTS13 deficiency. Recognize the classic features: fever, anemia (microangiopathic hemolytic), renal failure, thrombocytopenia, and CNS disease. (It is rare that all 5 manifestations are present in the clinical setting). Also recognize that the clinical scenario could include: a pregnant woman, h/o autoimmune disease (especially lupus), h/o metastatic cancer (especially adenocarcinomas), h/o certain chemotherapy agents, h/o post-stem cell transplant, or no symptoms (healthy patient). The presentation is similar to malignant hypertension and scleroderma renal crisis, but hypertension is not a feature in TTP.
Dx: Clinical + Required features: thrombocytopenia and microangiopathic hemolytic anemia (schistocytes) + PT/PTT (normal).
Tx: Immediate plasma exchange transfusion
ADAMTS13 deficiency.
TTP
Female patient with h/o multiple spontaneous abortions presents with:
An acute deep venous thrombosis
Holosystolic murmur at the apex
Violaceous, reticular rash on the thighs and arms (livedo reticularis and livedo racemosa).
↓ Platelets
Normal PT and prolonged PTT that does not correct with 1:1 mix with normal plasma
+ Serum VDRL
What is the diagnosis?
antiphospholipid syndrome (APS).
Explanation
The PTT in APS is sometimes considered “paradoxically prolonged” because the disease causes venous thrombosis, not bleeding.
Dx: Use clinical classification criteria (needs 1 clinical criterion [thrombosis or pregnancy morbidity] + 1 laboratory criterion [anticardiolipin antibody, anti-β2-glycoprotein 1 antibody, or lupus anticoagulant]), with repeat laboratory criteria assessed 12 weeks later.
Tx: Acute DVT is treated with a heparin product followed by indefinite lifetime anticoagulation with warfarin.
Healthy male develops community-acquired pneumonia and is given a β-lactam antibiotic. After 1 week, he develops:
Fatigue
Jaundice
Dark urine
↓ Hgb
↑ Reticulocyte count
Peripheral smear: Red cell fragments, bite cells, and Heinz bodies are seen when special Heinz body preparation is done.
Negative Coombs test
What is the most likely diagnosis? What is the etiology?
acute hemolysis due to glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Explanation
The history of infection prior to development of acute hemolysis is important and, together with characteristic “bite cells,” usually suggests the diagnosis. The negative Coombs test makes infection-associated autoimmune hemolytic anemia unlikely.
Dx: Clinical + measurement of serum G6PD 3 months after the acute hemolytic event. If done earlier, the G6PD level may be inappropriately high because reticulocytes formed in response to the hemolysis contain high levels of the enzyme.
Tx: Specific treatment depends on the type and extent of disease; all patients should avoid certain drugs that trigger hemolysis (e.g., dapsone, nitrofurantoin, primaquine, sulfa drugs, rasburicase) and eating fava beans.
Healthy patient presents with:
Mildly ↓ Hgb and MCV < 65 fL
Normal reticulocyte count, serum Fe, TIBC, ferritin, indirect bilirubin, haptoglobin, and LDH
Hemoglobin electrophoresis shows increased HbA2
What is the diagnosis?
β-thalassemia minor.
Explanation
Both α- and β-thalassemia are associated with microcytic anemias, but β-thalassemia is the one with the abnormal hemoglobin electrophoresis (increased A2 component).
Dx: Clinical and of exclusion (exclude iron deficiency anemia) + Hgb electrophoresis (increased HbA2, perhaps presence of HbF, and in severe thalassemia there is no Hgb A production).
Tx: None required; discontinue iron supplementation if appropriate.
Show Question
Young patient with h/o substance abuse presents with:
Confusion after using inhalants
↑ Heart rate
Pulse oximetry > 92%
Blood: Unusual chocolate-brown discoloration
PaO2 > 70 mmHg
What is the diagnosis? What is this due to?
acquired methemoglobinemia due to inhalation of nitrites.
Explanation
Remember the association between inhalation of amyl nitrite (slang terms = “poppers,” “rush,” “jungle juice”) and methemoglobinemia. Dapsone and local anesthetics are also associated with acquired methemoglobinemia.
Dx: Clinical (high suspicion if cyanotic and normal oxygenation) + arterial methemoglobin concentration.
Tx: Varies depending on etiology and concentration. For acquired cases with > 20% methemoglobin concentration, give methylene blue.
selective IgA deficiency is given a transfusion of packed red cells because of symptomatic anemia.
During the transfusion, she develops:
Shortness of breath
Wheezing
Hypotension
What is the diagnosis?
anaphylaxis to blood products.
Explanation
Patients with selective IgA deficiency can develop anti-IgA antibodies. When given blood products containing IgA, anaphylaxis can result. Definitely remember that anaphylaxis is a possibility if IgA-deficient patients
are given routine blood products.
Dx: Clinical.
Tx: Stop the transfusion immediately + IV fluids + epinephrine ± glucocorticoids.
trimethoprim/sulfamethoxazole for a sinus infection presents for follow-up:
Fatigue
↓ WBC, Hgb, Hct, Plt with normal MCV
↓ Reticulocyte count
Peripheral smear: Normal cell maturation but ↓ cell numbers
Bone marrow biopsy: Hypocellular marrow
What is the diagnosis? What is it caused by?
aplastic anemia caused by sulfa drug.
Explanation
If the patient were not taking TMP/SMX, a drug notoriously associated with aplastic anemia, the differential diagnosis would reasonably include myelodysplasia, myelofibrosis, paroxysmal nocturnal hemoglobinuria (PNH), and aplastic anemia due to viruses such as HBV. Other drugs that can cause aplastic anemia include valproic acid, phenytoin, NSAIDs, chloramphenicol, carbamazepine, and nifedipine.
Dx: Clinical (but bone marrow aspiration and biopsy may be performed).
Tx: Discontinuation of marrow-suppressing drug.
Elderly patient who has never had a bleeding problem presents with:
Recurrent epistaxis, hematuria, and large ecchymoses that develop without history of trauma
Normal CBC
Peripheral smear: No abnormalities
Normal bleeding time
Normal PT but prolonged PTT that does not correct with 1:1 mix with normal plasma after 60 minutes
What is the diagnosis?
Factor 8 inhibitor.
Severe bleeding, high titer inhibitor – For patients with higher titer factor VIII inhibitors (ie, ≥5 Bethesda units) and/or severe bleeding, we suggest the use of an activated prothrombin complex concentrate (aPCC; eg, factor VIII inhibitor bypassing activity [FEIBA]) or recombinant human factor VIIa [45,46]. Human factor VIII products generally cannot be given in high enough amounts to overcome the inhibitor. RecomExplanation
The bleeding and the prolonged PTT suggest a factor deficiency. The failure of the PTT to correct with the mixing study tells you that an inhibitor is present. You might have been thinking this was antiphospholipid syndrome (APS), which is associated with prolongation of PTT and does not correct with the mixing study. But remember that APS is associated with clotting, not bleeding. This is not von Willebrand’s because the bleeding time is normal and the mixing study does not correct (it does correct in von Willebrand’s disease when Factor 8 is replaced). Remember conditions associated with development of Factor 8 inhibitors: age > 50 years, pregnancy, RA, SLE, and underlying malignancy.
Dx: Clinical + PTT (prolonged) + 1:1 mix (fails to correct).
Tx: DDAVP® (desmopressin) ± Factor 8 concentrate for severe bleeds + immunomodulation to remove the inhibitor (systemic corticosteroids, steroids + cyclophosphamide, steroids + rituximab, or IVIG).
heumatoid arthritis has:
↓ Hgb and Hct, normal MCV and MCHC
↓ Reticulocyte count
↓ Serum Fe, ↓ TIBC, normal Fe/TIBC, ↑ ferritin, normal soluble transferrin receptor
Normal WBC, Plt, indirect bilirubin, haptoglobin, and LDH
What is the cause of the anemia?
anemia is inflammation (sometimes called anemia of chronic disease [ACD]).
Explanation
Note that this anemia can occur with any chronic disease, such as rheumatoid conditions, chronic infections, and cancers.
Dx: Iron studies (serum Fe, TIBC, ferritin, Fe/TIBC) ± soluble transferrin receptor assay.
Tx: Treat underlying condition.
broad-spectrum antibiotic for treatment of an infection. He then develops:
Epistaxis and large ecchymoses at injection sites
Normal CBC
Peripheral smear: No abnormalities
Prolonged PT but normal PTT
Normal AST and ALT
Normal or slightly reduced albumin
What is the cause of the coagulopathy? What is this due to?
Broad-spectrum antibiotics eradicate the vitamin K-producing organisms from the intestine and lead to deficiency.
Dx: Clinical + PT (prolonged) + platelets (normal).
Tx: Support and discontinuation of antibiotic or change to an antibiotic with a more narrow spectrum of activity + vitamin K replacement.
Pregnant patient with a family history of deep venous thrombosis presents with:
Acute DVT
She is most likely to have 1 of 2 common inherited thrombophilias. What are the 2?
The 2 thrombophilias are activated protein C (APC) resistance and prothrombin gene mutation.
Explanation
APC resistance is the disease caused by Factor 5 Leiden mutation. The G20210A mutation is the mutation in the prothrombin gene.
Dx: Clinical suspicion + functional assay + gene testing.
Tx: Anticoagulation.
↓Hgb and Hct with ↓ MCV and MCHC
↓ Reticulocyte count
↓ Serum Fe, ↑ TIBC, Fe/TIBC < 20%, ↓ ferritin, ↑ soluble transferrin receptor concentration
What is the diagnosis
ron deficiency anemia (IDA).
Fatigue, gingival bleeding, and epistaxis
Prolonged PT and PTT
↑ D-dimer and fibrin degradation products; ↓ fibrinogen
Peripheral smear: Promyelocytes with red, rod-like structures in the cytoplasm; myeloperoxidase+
Cytogenetics: t(15;17) translocation
What is the diagnosis?
DIC in the setting of acute promyelocytic leukemia (aPML or AML M3 type).
Explanation
This script includes a coagulopathy due to the presence of disseminated intravascular coagulation (DIC), which is most commonly seen in aPML. This is an important script to remember: When AML M3 presents with DIC, urgent prescription of an all-trans retinoic acid (ATRA) drug is necessary because aPML is 1 of the most malignant forms of AML (even though it is also 1 with the best prognosis when treated). The t(15;17) translocation is 1 of the molecular clues to the diagnosis of aPML.
Dx: CBC or marrow biopsy showing characteristic promyelocytes ± Auer rods + flow cytometry/cytogenics + evidence of DIC.
Tx: Immediate ATRA-based chemotherapy.
