3 Consultative Hematology Flashcards
The most common type of anemia in outpatients
Iron-deficiency anemia
The most common type of anemia in hospitalized patients
Anemia of chronic inflammation
The most common source of occult blood loss in
Men:
Women:
Men: gastrointestinal tract
Women: blood loss secondary to menorrhagia
Evaluation of anemia
Of the RBC indices, the ______ is most useful.
MCV
- Microcytic (MCV < 80 fL)
- Normocytic (MCV 80–100 fL)
- Macrocytic (MCV > 100 fL)
Useful in evaluating whether anemia is from decreased RBC production by the marrow versus increased destruction
Reticulocyte index
- Low reticulocyte index [< 2.0]
- High reticulocyte index [≥ 2.0]
TRUE OR FALSE
Red cell size is best assessed from the MCV because the blood film is a 2-dimensional assessment of a 3-dimensional question (volume).
TRUE
Red cell size is best assessed from the MCV because the blood film is a 2-dimensional assessment of a 3-dimensional question (volume).
Causes of microcytic anemia
- Iron deficiency
- Thalassemia minor
- Sideroblastic anemia (hereditary, lead poisoning)
Causes of normocytic anemia
- Anemia of chronic inflammation
- Anemia of chronic kidney disease
- Primary marrow disorders
- Hemolytic anemias
Toxin causing normocytic anemia, basophilic stippling of the erythrocytes may be fine or course with a variable number of granules in each cell
Lead poisoning
Causes of macrocytic anemia
- Deficiencies of folate and vitamin B12
- Acute megaloblastic anemia
- Drug induced
- Alcohol abuse
- Inborn errors of metabolism
- Clonal hematologic disorders including myelodysplastic syndromes
Neutropenia refers to values less than 2 SD below the normal mean of the population, and corresponds to
Children 1-10yo:
Above 10 yo:
Children 1-10: less than 1.5 × 109/L
Above 10: less than 1.8 × 109/L
An inherited cause of neutropenia in individuals of African descent and certain other ethnic groups in which the mean and 95% confidence interval of ANC is significantly lower than that of persons of European descent
Benign ethnic neutropenia
Neutropenia in persons of European descent may be mild (ANC <1.8 × 109/L), moderate (ANC <1.0 × 109/L), or severe (ANC <0.5 × 109/L).
Causes of chronic neutropenia
- (a) congenital neutropenia (neutropenia present at or near birth secondary to a marrow failure syndrome primarily involving the granulocytic series);
- (b) cyclic neutropenia (a rare autosomal-dominant genetic disorder characterized by neutropenia that recurs every 14 to 35 days);
- (c) chronic idiopathic neutropenia (no obvious cause for the neutropenia; ANC ranges from 0.5 to 1.0 × 109/L);
- (d) chronic infections (particularly hepatitis and HIV);
- (e) nutritional deficiencies (vitamin B12, folate, or copper); and
- (f) autoimmune disorders
With respect to autoimmune disorders, nearly half of patients with systemic lupus erythematosus (SLE) have neutropenia, often with accompanying monocytopenia and lymphopenia.
Thrombocytopenia is defined in adults as being below the lower limit of normal (150 × 109/L),
Mild:
Moderate :
Severe:
- Mild: (70–150 × 109/L)
- Moderate : (20–70 × 109/L)
- Severe: (< 20 × 109/L)
Causes of thrombocytopenia
- Impaired platelet production
- Increased platelet destruction
- Abnormal distribution
A finding of more than 10% megathrombocytes (platelets greater in diameter than one-third of a red cell diameter) suggests
Immune platelet destruction
It usually occurs 5–10 days after exposure to heparin and is associated with both venous and arterial thrombosis.
The thrombocytopenia can be mild, and bleeding is unusual.
HIT
The specifics of diagnostic tests, including an immunoassay for antiplatelet factor-4
In a patient with neurologic symptoms, microangiopathic hemolysis, and an elevated serum creatinine, ____________ should be ordered in addition to instituting prompt plasmapheresis for the tentative diagnosis of TTP.
A disintegrin and metalloprotease with a thrombospondin type 1 motif member 13 (ADAMTS-13) activity level
Causes of thrombocytopenia in pregnancy
- Preeclampsia
- HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome
- Abruptio placentae with DIC
Acquired and Congenital Causes of Pancytopenia
Acquired
* Marrow infiltration/replacement
* Marrow aplasia
* Blood cell destruction/sequestration/redistribution
* Combination of causes
Congenital
* Wiskott-Aldrich syndrome
* Fanconi anemia, dyskeratosis congenita
* Shwachman-Diamond syndrome
* GATA2 deficiency
* Hemophagocytic lymphohistiocytosis
Refers to an increase in hemoglobin concentration
Erythrocytosis
Relative erythrocytosis: erythrocytosis may be caused by a decrease in plasma volume
Absolute erythrocytosis: an increase in the RBC mass
The most common reasons for a decrease in plasma volume
Dehydration from vomiting, diarrhea, or diuretic use
Causes of absolute erythrocytosis
- Acquired or hereditary autonomous production of RBCs (primary erythrocytosis)
- Acquired or hereditary appropriate physiologic response to an increased production of serum erythropoietin (EPO) (secondary erythrocytosis)
- Disorders of hypoxia signaling
Myeloid neoplasm in which the increased red cell mass frequently accompanies an increase in granulocytes and platelets
Associated with Janus kinase 2 (JAK2) mutations
PV
The findings of splenomegaly, thrombocytosis, and/or granulocytosis are highly suggestive of PV and should trigger mutational testing for JAK2V617F (exon 14), and if the findings are negative, JAK2 exon 12 mutation.
Most common causes of secondary erythrocytosis
(a) cardiopulmonary states that lead to hypoxemia,
(b) carboxyhemoglobinemia resulting from smoking or toxic exposure,
(c) autonomous EPO production from malignancies or polycystic kidney disease, and
(d) exogenous EPO administration (“blood doping”)
Neutrophilia refers to an increase in the band and segmented neutrophils to a combined concentration greater than 2 SD above the normal population mean value, or approximately__________ × 109/L
7.5 × 109/L
Most common cause of neutrophilia
Inflammatory and infectious diseases
Other secondary causes of neutrophilia include smoking, obesity, stress (both physical and emotional), asplenia, and medications
Primary marrow disorders associated with neutrophilia
- Chronic myelogenous leukemia (CML)
- Other myeloproliferative neoplasms
- Chronic neutrophilic leukemia (CNL)
- Sickle cell disease
In a patient with persistent neutrophilia of unclear etiology, it is generally advisable to exclude CML with a qualitative breakpoint cluster region-Abelson (BCR-ABL) polymerase chain reaction (PCR) analysis.
CNL, a rare disorder can be considered when the WBC must be greater than ________ with greater than 80% neutrophils
Splenomegaly is a very frequent feature
25 × 109/L
Genetic testing for the_________ gene mutation, present in approximately 90% of cases, is confirmatory of CNL
CSF3R
Medications that cause neutrophilia
- Glucocorticoids
- Lithium
- Exogenous growth factors such as granulocyte colony-stimulating factor
Eosinophilia
Mild
Moderate
High
Eosinophilia
* Mild (< 1.0 × 109/L)
* Moderate (1.0–5.0 × 109/L)
* High (> 5.0 × 109/L)
The normal absolute eosinophil count is less than 0.4 × 109/L.
The most common cause of eosinophilia
Infection with helminthic parasites
In industrialized countries, the allergic diseases (allergic rhinitis, atopic dermatitis, and asthma) are the most common causes with mild to moderate degrees of eosinophilia.
Rhinosinusitis, asthma, and eosinophilia require screening for
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
Basophils are the least common of the circulating WBCs, and typically account for less than ___________ % of blood leukocytes.
Less than 0.5–1%
Basophilia may be associated with:
* Allergic or inflammatory responses
* Endocrinopathies (diabetes, myxedema)
* Infections (chicken pox, influenza, smallpox, tuberculosis)
* Iron deficiency
* Clonal myeloid diseases (especially CML, but also PV, primary myelofibrosis, ET, acute myelogenous leukemia [AML], and basophilic leukemias)
TRUE OR FALSE
If the medical history, physical examination, or laboratory findings do not support other potential etiologies, CML should be considered as virtually all patients have basophilia.
TRUE
If the medical history, physical examination, or laboratory findings do not support other potential etiologies, CML should be considered as virtually all patients have basophilia.
The usual presenting skin lesion in mastocytosis appearing as small yellowish tan to reddish-brown macules or papules
Urticaria pigmentosa
Monocytosis in adults is present when the absolute count exceeds_____ × 109/L
0.8 × 109/L
The causes of monocytosis include:
* Myeloid and lymphoid neoplasms
* Chronic and drug-induced neutropenia
* Immune hemolytic anemia
* A variety of inflammatory and immune disorders
* Infections
* Gastrointestinal disorders
* Following a myocardial infarction
* Postsplenectomy
Unexplained monocytosis, particularly in elderly patients with other cytopenias, should raise concern for myeloid malignancies, such as__________________ , and generally warrants examination of the marrow.
MDS and chronic myelomonocytic leukemia (CMML)
In adults, lymphocytosis refers to an ALC that exceeds ________× 109/L
4 × 109/L
*The normal absolute lymphocyte count (ALC) is higher in children than adults. *
Primary lymphocytosis disorders include:
- Acute and chronic lymphocytic leukemia
- Prolymphocytic leukemia
- Hairy cell leukemia
- The leukemic phase of B-cell lymphoma
- Large granular lymphocytic leukemias (LGLLs)
Reactive lymphocytosis is most commonly caused by
- Infectious mononucleosis (presenting symptoms may include fever and tonsillary pharyngitis with cervical lymphadenopathy)
- Bordetella pertussis
- Natural killer (NK) cell lymphocytosis
- Stress (cardiovascular collapse, toxic shock, trauma, major surgery)
- Hypersensitivity reactions to insects or drugs
- Subacute or chronic persistent lymphocytosis from conditions such as smoking, hyposplenism, chronic infections, or thymoma
There are 4 main causes of thrombocytosis:
- (a) clonal
- (b) reactive (secondary)
- (c) familial
- (d) spurious
Causes of spurious thrombocytosis
- Mixed cryoglobulinemia
- Fragmented red blood cells
- Bacteria
Familial thrombocytosis caused by mutations in the gene for the thrombopoietin receptor, ______, the thrombopoietin gene ______
Thrombopoietin receptor: MPL
Thrombopoietin gene : THPO
TRUE OR FALSE
Blast cells in the blood are nearly always indicative of a hematopoietic neoplasm.
TRUE
Blast cells in the blood are nearly always indicative of a hematopoietic neoplasm.
In inflammatory reactions, promyelocytes are rare and myelocytes infrequent.
Causes for the appearance of nRBCs (normoblasts) in the blood
(a) hypoxia from various cardiopulmonary causes,
(b) stress erythropoiesis (eg, severe hemolytic anemia), and
(c) a myelophthisic condition
A leukoerythroblastic blood film (nRBCs, teardrop RBCs, myeloid immaturity, giant platelets) is a significant clue of marrow infiltration and extramedullary hematopoiesis.
The most frequent indications for referral of lymphadenopathy
- Nodes larger than 2 cm
- The presence of enlarged supraclavicular nodes (up to 50% risk of malignancy in some series),
- When there are no signs of resolution within a few weeks
LADs: Remains the gold standard, but multiple wide diameter core biopsies are a reasonable alternative
Excision biopsy
** Multiple wide diameter core** biopsies are a reasonable alternative.
Narrow core biopsies and fine-needle aspirations should be discouraged if there is the likelihood of a lymphoma.
Causes of massive splenomegaly
- Myeloproliferative disorders (primary myelofibrosis, CML)
- Leukemias (hairy cell and CLL)
- Infections (malaria, leishmaniasis)
- Thalassemia major
- Gaucher disease
Monoclonal gammopathy
Immunoglobulin G (IgG) and IgA:
Immunoglobulin M:
Immunoglobulin G (IgG) and IgA: myeloma, amyloidosis, or lymphoma
Immunoglobulin M: lymphoma or Waldenström macroglobulinemia
Patients with a monoclonal immunoglobulin or light chain in the absence of a malignancy have
Essential monoclonal gammopathy
Diseases associated with a polyclonal gammopathy
- Liver disease (cirrhosis, autoimmune or viral hepatitis)
- Connective tissue disorders
- Infections (bacterial, osteomyelitis, endocarditis, viral including HIV)
- Hematologic disorders (non-Hodgkin lymphoma, chronic CLL, thalassemia, sickle cell disease)
- Nonhematologic malignancies (lung, ovarian, gastric, hepatocellular)
Describes nonblanchable, hemorrhagic skin or mucosal lesions that are a result of bleeding under the surface of the skin
Petechiae (< 2 mm)
Ecchymoses (≥ 2 mm)
An acute life-threatening disorder resulting from microvascular thrombosis and hemorrhagic infarction
A result of severe disseminated intravascular coagulation (eg, as a complication of meningococcal or streptococcal sepsis)
A consequence of congenital protein C or S deficiency.
Painful lesions are distinguishable by central areas of blue-black hemorrhagic necrosis with a surrounding erythematous border
Purpura fulminans
The most common cause of vasculitis in children, with the purpura tending to be on the buttocks and lower extremities, plus other clinical signs of arthritis, abdominal pain, and nephritis
Henoch-Schönlein purpura
The most common cause of acquired platelet dysfunction
Aspirin
The most common hereditary causes of VTE
- Factor V Leiden (FVL)
- Prothrombin 20210 mutation
Spontaneous upper-extremity VTE
Thoracic outlet syndrome
Unprovoked left iliofemoral DVT, particularly in women between 20 and 50 years of age
May-Thurner syndrome
If a D-dimer assay is positive or unavailable, compression ultrasonography with Doppler should be performed, and if negative, repeated in _____ days.
5–7 days
A PE occurs in up to ________of patients with a ________________ vein thrombosis.
In contrast, a clinically important PE is rarely (1% or less) associated with a thrombosis confined to the calf veins.
50%
Proximal vein thrombosis
Used to establish or exclude the diagnosis of PE with high predictive value of PE
Computerized tomographic angiography (CTA) or combined CTA-computed tomographic venography
Characterized by venous or arterial thrombosis or pregnancy complications attributed to placental insufficiency in the presence of persistent laboratory evidence of antiphospholipid antibodies (aPLs)
APS
The presence of aPLs alone is insufficient for the diagnosis
in APS, 50% of patients will have a DVT of the ________________
DVT of the lower extremity
25% of patients present with an arterial thrombosis
25% both venous and arterial thromboses
An infrequent presentation of APS characterized by severe, widespread vascular occlusions in at least 3 organs, systems, and/or tissues; development of manifestations simultaneously or in less than 1 week; histopathologic confirmation of small-vessel occlusion; and laboratory evidence of the presence of aPLs
Catastrophic antiphospholipid syndrome (CAPS)
The laboratory diagnosis of APS requires the demonstration of aPLs and/or antibodies against relevant protein cofactors by immunoassays or coagulation tests performed__________weeks apart
12 or more weeks
Evaluation for a hereditary cause of thrombophilia is warranted in select populations, including:
(a) patients with at least 1 first-degree relative with documented VTE before the age of 45 years
(b) patients without a family history who are younger than 45 years of age, have recurrent thrombosis or thrombosis in multiple sites, or a history of warfarin-induced skin necrosis
A febrile illness with anemia, thrombocytopenia, and multiorgan involvement (including splenomegaly, hepatitis, coagulation abnormalities, mental status changes).
A very high serum ferritin ranging from 500 to 10,000 mg/mL
Hemophagocytic lymphohistiocytosis (HLH)
Infections, most commonly an Epstein-Barr viral infection, can disrupt immune homeostasis and lead to this aggressive and life-threatening syndrome.
The most useful test to discern iron overload from other causes
Transferrin saturation (TSAT)
Ratio of serum iron to the total iron-binding capacity (TIBC)
TSAT, 45% or greater in men and 40% or greater in women is likely caused by iron overload
The most common cause of hereditary hemochromatosis is caused by what mutation
HFE gene
Many clinicians consider tissue biopsy as the “gold standard” for diagnosi
The most common abnormalities associated with VTE in pregnancy
FVL and PGM
Normal physiologic changes in pregnancy
(a) increased levels of fibrinogen and factors II, VII, VIII, and X;
(b) decreased protein S activity from reductions in total and free protein S antigen
(c) decreased protein C activity because of decreased activity of protein S (a cofactor for protein C) and increased factor VIII activity
(d) increased levels and activity of the fibrinolytic inhibitors, thrombin-activatable fibrinolytic inhibitor, and plasminogen activator inhibitor types 1 and 2
2-7-8-10, S
TRUE OR FALSE
As D-dimer levels rise with a normal pregnancy, they may not be useful in excluding VTE; in such case, diagnostic imaging is required.
TRUE
As D-dimer levels rise with a normal pregnancy, they may not be useful in excluding VTE; in such case, diagnostic imaging is required.
TRUE OR FALSE
All women with a prior history of VTE should be offered postpartum prophylaxis; those with a high risk of recurrence should receive antepartum prophylaxis.
TRUE
All women with a prior history of VTE should be offered postpartum prophylaxis; those with a high risk of recurrence should receive antepartum prophylaxis.
A life-threatening condition of pregnancy in which a consumptive thrombocytopenia is accompanied by microangiopathic hemolysis and hepatic dysfunction.
Most patients are diagnosed between 27 and 37 weeks of pregnancy
HELLP syndrome
Risk factors for HELLP
- European ancestry
- Multiparity
- Maternal age older than 34 years
- Personal or familiar history of HELLP syndrome
The most common presenting symptom of HELLP
Abdominal pain
