ABPath Hematopathology cheat sheet

Bone marrow cellularity is estimated as 100 minus patient age in years; a 60-year-old has roughly 40% cellularity.

The myeloid-to-erythroid ratio is normally 2:1 to 4:1; it rises with granulocytic hyperplasia and falls with erythroid hyperplasia.

Prussian blue iron stores are graded 0 to 4; grade 0 is absent, grade 2 is normal, and grades 3 to 4 indicate increased iron.

Reticulin fibrosis is graded MF-0 to MF-3; MF-2 shows diffuse dense reticulin, and MF-3 adds collagen fibrosis or osteosclerosis.

Dysplasia requires at least 10% dysplastic cells in one or more lineages; specific MDS subtypes require ring sideroblasts or excess blasts.

Blast percentage is determined from a 500-cell differential; at least 20% blasts generally defines acute leukemia, except APL with t(15;17).

Karyotyping requires 20 metaphases; common FISH probes include BCR::ABL1 t(9;22), PML::RARA t(15;17), RUNX1::RUNX1T1 t(8;21), and CBFB::MYH11 inv(16).

Flow cytometry identifies blasts as CD45 dim and CD34 positive; MPO, CD3, CD19, and CD20 support lineage assignment.

EDTA blood smears are best prepared within 2 to 4 hours; citrate is used for coagulation testing, and marrow aspirate is preferred over decalcified biopsy for morphology and flow.

Hematopoiesis begins in the yolk sac at about 3 weeks, transitions to the liver by 6 weeks, and moves to bone marrow by 20 weeks of gestation.

Hemoglobin switching proceeds from embryonic hemoglobins to fetal HbF (alpha2 gamma2) and then to adult HbA (alpha2 beta2); adult HbF is below 1% to 2%.

Erythropoietin from renal peritubular cells drives erythropoiesis and is regulated by HIF-2 alpha; thrombopoietin from the liver drives megakaryopoiesis.

CD34 marks hematopoietic stem and progenitor cells; lineage markers include CD19 for B cells, CD3 for T cells, CD13/CD33 for myeloid cells, and CD41/CD61 for megakaryocytes.

Granulopoiesis takes about 10 to 14 days; the marrow granulocyte reserve is roughly 10 times the circulating pool and is mobilized by stress.

Clonal hematopoiesis of indeterminate potential is defined by a somatic mutation with variant allele frequency at least 2% without cytopenia or dysplasia; common genes are DNMT3A, TET2, and ASXL1.

Marrow adipocytes increase with age; red marrow converts to yellow marrow in long bones, and red marrow reconversion occurs with severe anemia.

B lymphocytes mature in bone marrow, T lymphocytes mature in the thymus, and natural killer cells arise from the common lymphoid progenitor.

Anemia is hemoglobin below 13 g/dL in men and below 12 g/dL in women; reticulocyte index equals reticulocyte percentage times patient hematocrit divided by normal hematocrit.

Microcytic anemia with MCV below 80 fL suggests iron deficiency, thalassemia, anemia of chronic disease, or sideroblastic anemia; ferritin and hemoglobin electrophoresis help distinguish them.

Iron deficiency is supported by ferritin below 30 ng/mL, elevated soluble transferrin receptor, high RDW, and often thrombocytosis.

Anemia of chronic disease shows low serum iron, low TIBC, normal or high ferritin, and low transferrin saturation due to hepcidin-mediated iron sequestration.

Warm autoimmune hemolytic anemia is IgG mediated, DAT positive for IgG, and associated with spherocytes; cold agglutinin disease is IgM and complement mediated.

Paroxysmal nocturnal hemoglobinuria is diagnosed by flow cytometry showing loss of CD55 and CD59 on red cells and loss of CD24 or CD14 on granulocytes.

G6PD deficiency shows Heinz bodies and bite cells; testing during reticulocytosis may be falsely normal because young red cells have higher enzyme activity.

Sickle cell disease is confirmed by hemoglobin electrophoresis showing HbS; chronic hemolysis and vaso-occlusion are treated with hydroxyurea to raise HbF.

Megaloblastic anemia shows high MCV, hypersegmented neutrophils, and low B12 or folate; methylmalonic acid is elevated in B12 deficiency.

Absolute neutrophil count equals white blood cell count times the percentage of segmented plus band neutrophils; severe neutropenia is below 500/microliter.

Chronic myeloid leukemia is defined by t(9;22) forming BCR::ABL1; the smear shows basophilia and a full myeloid left shift, and chronic phase has fewer than 10% blasts.

Acute myeloid leukemia is diagnosed at 20% or more blasts in blood or marrow, except APL with t(15;17), which is diagnostic regardless of blast count.

Acute promyelocytic leukemia has t(15;17) PML::RARA, frequent DIC and Auer rods, and requires urgent ATRA plus arsenic trioxide.

Myelodysplastic syndromes show cytopenia, dysplasia in at least 10% of one or more lineages, and fewer than 20% blasts; ring sideroblasts at 5% or more with SF3B1 support a specific subtype.

Chronic myelomonocytic leukemia shows monocytosis at least 1 x 10^9/L, fewer than 20% blasts, and dysplasia; it is an MDS/MPN overlap disorder.

A leukemoid reaction has white blood cells above 50,000/microliter, a left shift, toxic granulation, and high leukocyte alkaline phosphatase, unlike CML.

Flow markers include CD13, CD33, MPO, and CD117 for myeloid blasts; CD19, CD22, and CD79a for B lymphoblasts; and cytoplasmic CD3 and CD7 for T lymphoblasts.

Chronic granulomatous disease is diagnosed by an abnormal DHR or NBT oxidative burst test and causes recurrent catalase-positive bacterial and fungal infections.

Chronic lymphocytic leukemia is CD5 positive, CD23 positive, CD20 dim, and surface immunoglobulin dim; an absolute clonal B-cell count of at least 5 x 10^9/L is required.

Mantle cell lymphoma is CD5 positive, CD23 negative, cyclin D1 positive, and has t(11;14); it is generally more aggressive than CLL.

Follicular lymphoma is CD10 positive, BCL2 positive, and has t(14;18) IGH::BCL2; it usually has an indolent course.

Hairy cell leukemia expresses CD11c, CD25, CD103, and CD123, is TRAP positive, and commonly has BRAF V600E; pancytopenia and splenomegaly are typical.

Burkitt lymphoma has t(8;14) involving MYC, a Ki-67 near 100%, starry-sky histology, CD20 positivity, and TdT negativity.

Classic Hodgkin lymphoma has Reed-Sternberg cells that are CD15 positive, CD30 positive, CD45 negative, and PAX5 weak; nodular sclerosis is the most common subtype.

Plasma cell myeloma requires at least 10% clonal plasma cells plus CRAB features or myeloma-defining events; cells are CD138 positive and CD38 positive.

Waldenstrom macroglobulinemia shows an IgM M spike, lymphoplasmacytic infiltrate, and MYD88 L265P mutation; hyperviscosity may occur.

T-cell large granular lymphocytic leukemia is CD3 positive, CD8 positive, CD57 positive, often STAT3 mutated, and associated with neutropenia and rheumatoid arthritis.

Aplastic anemia shows pancytopenia with hypocellular marrow; cellularity is below 25%, or below 30% with less than 50% residual hematopoietic cells.

Primary myelofibrosis causes a leukoerythroblastic smear, teardrop cells, splenomegaly, and reticulin fibrosis; JAK2, CALR, or MPL mutations are common.

Hemophagocytic lymphohistiocytosis requires five of eight criteria, including fever, splenomegaly, cytopenias, hypertriglyceridemia or hypofibrinogenemia, hemophagocytosis, low NK activity, high ferritin, and high sIL-2R.

Systemic mastocytosis shows CD117-positive mast cells, KIT D816V mutation, and elevated tryptase; anaphylaxis is a major risk.

Bone marrow metastasis often appears as cohesive carcinoma clusters causing myelophthisis; neuroblastoma may form rosettes in children.

Gaucher disease shows Gaucher cells with crumpled tissue-paper cytoplasm due to glucocerebrosidase deficiency; bone pain and hepatosplenomegaly are common.

Bone marrow necrosis can result from malignancy, infection, or sickle cell disease and generally indicates a poor prognosis.

Graft-versus-host disease after transplantation affects skin, gastrointestinal tract, and liver; biopsy shows apoptotic bodies and epithelial damage.

Thrombocytopenia is a platelet count below 150 x 10^9/L; severe thrombocytopenia is below 50 x 10^9/L, and bleeding risk rises below 20 x 10^9/L.

Immune thrombocytopenia is isolated thrombocytopenia without another cause; treatment is usually given when platelets are below 30 x 10^9/L or bleeding is present.

Thrombotic thrombocytopenic purpura has ADAMTS13 activity below 10%; urgent plasma exchange is indicated, and platelet transfusion is avoided unless bleeding is life-threatening.

Heparin-induced thrombocytopenia is caused by PF4-heparin antibodies, causes a platelet drop greater than 50%, and paradoxically causes thrombosis; heparin is stopped and a non-heparin anticoagulant is used.

Glanzmann thrombasthenia is a glycoprotein IIb/IIIa deficiency with normal platelet count and absent aggregation to all agonists except ristocetin.

Bernard-Soulier syndrome is a glycoprotein Ib-IX-V deficiency with giant platelets and absent ristocetin aggregation.

von Willebrand disease shows prolonged PFA-100 or bleeding time and low von Willebrand factor antigen or activity; desmopressin is used for type 1 disease.

Essential thrombocythemia has platelets above 450 x 10^9/L, JAK2, CALR, or MPL mutation, and megakaryocyte proliferation; aspirin reduces vascular risk.

Prophylactic platelet transfusion is generally given below 10 x 10^9/L, below 50 x 10^9/L for surgery, and below 100 x 10^9/L for central nervous system surgery.

PT measures extrinsic and common pathway factors (VII, X, V, II, fibrinogen); aPTT measures intrinsic and common pathway factors (VIII, IX, XI, XII, X, V, II).

INR equals (patient PT divided by normal PT) raised to the ISI power; warfarin is monitored by INR with a target of 2 to 3 for most indications.

A mixing study that corrects indicates factor deficiency; failure to correct indicates an inhibitor such as a lupus anticoagulant or factor inhibitor.

Hemophilia A shows low factor VIII, prolonged aPTT, and normal PT; it is X-linked and treated with factor VIII replacement.

von Willebrand disease shows low von Willebrand factor activity, prolonged PFA-100, and abnormal ristocetin cofactor; type 1 is the most common form.

Factor V Leiden causes activated protein C resistance from a G1691A mutation and is the most common inherited thrombophilia.

Antiphospholipid syndrome is defined by lupus anticoagulant, anticardiolipin, or anti-beta2 glycoprotein I antibodies with thrombosis or pregnancy loss; triple positivity confers high risk.

Disseminated intravascular coagulation shows prolonged PT and aPTT, low fibrinogen, elevated D-dimer, thrombocytopenia, and schistocytes.

Direct oral anticoagulants include dabigatran, a thrombin inhibitor, and rivaroxaban or apixaban, factor Xa inhibitors; idarucizumab reverses dabigatran.

Restrictive red cell transfusion uses a hemoglobin threshold below 7 g/dL for stable hospitalized adults and below 8 g/dL for cardiac surgery or symptomatic coronary disease.

Prophylactic platelet transfusion is generally given below 10 x 10^9/L; it is avoided in TTP and HIT unless active bleeding is present.

Common critical values include hemoglobin below 7 g/dL, platelets below 20 x 10^9/L, white blood cells below 1.0 or above 50 x 10^9/L, and INR above 5.

Peripheral smear review is indicated for flagged CBC results, unexplained cytopenia, blasts, schistocytes, or suspected malaria.

EDTA-induced platelet clumping, hemolysis, and lipemia are common preanalytical errors; repeat testing in citrate or heparin may resolve the issue.

Delta checks compare current results with prior values; a large unexpected change prompts review for laboratory error or true clinical change.

After iron therapy, ferritin may rise and the reticulocyte response peaks at 7 to 10 days; this helps confirm iron deficiency.

Bone marrow flow cytometry and cytogenetics should be sent promptly when blasts or unexplained cytopenia are present; APL treatment must not be delayed for confirmatory testing.

Anticoagulation reversal uses vitamin K or prothrombin complex concentrate for warfarin, idarucizumab for dabigatran, and protamine for heparin.