Family Medicine: Hematology

Hemolytic Anemia

Decreased hemoglobin and haptoglobin. Increased reticulocytes, LDH, and indirect bilirubin

-RBCs are destroyed faster than they can be made

Direct Coombs

What is the first test to distinguish immune from non-immune hemolysis?

AIHA

Hemolytic anemia with a positive Direct Coombs test, increased reticulocytes, increased LDH, increased indirect bilirubin, and decreased haptoglobin

Hereditary Spherocytosis

Hemolytic anemia with + osmotic fragility/EMA binding test, spherocytes on smear, increased MCHC, splenomegaly, and pigmented gallstones

Folate

What needs to be supplemented in a patient with hereditary spherocytosis?

Corticosteroids

What is the treatment of choice for AIHA?

Vitamin B12 Deficiency

Macrocytic anemia (MCV > 100 fL)

-Causes: pernicious anemia, vegan diet, terminal ileum disease, bariatric surgery, chronic PPI/metformin use

-Presentation: paresthesia, decreased vibration, ataxia, dementia, glossitis

-Labs: decreased B12, increased MMA, increased homocysteine, hypersegmented neutrophils

-Tx: IM B12 daily x 7 days then weekly x 4 weeks, then monthly for life

Folate Deficiency

Macrocytic anemia (MCV > 100 fL)

-Causes: alcohol use disorder, poor diet, malabsorption, pregnancy, folate antagonists (methotrexate, bactrim, phenytoin, and sulfasalazine)

-Presentation: no neuro symptoms

-Labs: decreased RBC folate, increased homocysteine, normal MMA

-Tx: oral folic acid

B12, Folate Deficiency

What are the two types of megaloblastic anemia?

Non-megaloblastic

What types of macrocytic anemia are being described?

-Alcohol use disorder, liver disease, hypothyroidism, reticulocytosis, MDS, and drug-induced

Thalassemia, iron deficiency, chronic disease, sideroblastic

What are the most common causes of microcytic anemia?

GI blood loss, menstrual blood loss, dietary

What are the most common causes of iron deficiency anemia worldwide in these age groups?

-Men and postmenopausal women →

-Premenopausal women →

-Children/infants →

Iron Deficiency Anemia

Most common cause of microcytic anemia

-Presentation: fatigue, exertional dyspnea, palpitations, headache, tinnitus, restless legs, pallor, glossitis, angular cheilitis, pica, koilonychia

-Labs: decreased ferritin, serum iron, transferrin saturation / increased TIBC and RDW

-Tx: oral ferrous sulfate 325 mg 1-3 times daily on an empty stomach with vitamin C

Anemia of Chronic Disease

Microcytic anemia due to chronic inflammation, infection, malignancy, CKD when hepcidin sequesters iron in macrophages

-Labs: decreased serum iron, TIBC, and increased/normal ferritin

Lead Poisoning

What is a common cause of microcytic anemia in children?

-See basophilic stippling on smear. May be related to behavioral changes

Sideroblastic Anemia

What type of microcytic anemia is described as having ringed sideroblasts in marrow, increased ferritin and serum iron, and decreased TIBC?

Normocytic Anemia

Anemia with MCV 80-100 fL, which can be further classified as a production problem (low retic count) or hemolysis/blood loss (high retic count)

Decreased Erythropoietin

What lab value is indicative of anemia of chronic kidney disease?

Pancytopenia

What are the classic lab values seen in aplastic anemia?

ESA

What should be given for CKD anemia to replete iron stores?

ITP

An autoimmune disorder in which IgG autoantibodies bind to platelet glycoprotein receptors, leading to splenic destruction of platelets and impaired thrombopoiesis. Considered a diagnosis of exclusion

-Typically acute and follows a viral illness in children, chronic in adults, and can be associated with HIV/HCV/H.pylori/SLE/CLL

-Presentation: mucocutaneous bleeding, petechiae, purpura, bruising, epistaxis, heavy menses

-Dx: isolated thrombocytopenia with otherwise normal CBC, normal coagulation studies

-Tx: observation if platelets > 30,000 or corticosteroids if < 30,000

Steroids

What is the treatment of choice for ITP?

TTP

Life-threatening thrombotic microangiopathy caused by severe deficiency of ADAMTS13, which is either acquired or congenital

-Presentation: fever, anemia (schistocytes), thrombocytopenia, renal involvement (rise in Cr), neurologic symptoms

-Triggers: idiopathic, pregnancy, quinine, clopidogrel, cyclosporine/tacrolimus, HIV, autoimmune disease, malignancy

-Dx: schistocytes on smear + thrombocytopenia + normal PT/PTT, increased LDH, decreased haptoglobin, and negative direct Coombs test

-Tx: plasmapheresis, corticosteroids, avoid platelet transfusion

Plasmapheresis + Corticosteroids

What are the two hallmarks of TTP treatment?

HUS

Thrombocytopenia + MAHA + renal failure in children after bloody diarrhea

-Do not give abx

von Willebrand Disease

Most common inherited bleeding disorder, which is typically autosomal dominant, that’s due to a deficiency of vWF. This factor bridges platelets to subendothelial collagen and stabilizes factor VIII in plasma

-Presentation: epistaxis, easy bruising, heavy menses, postpartum hemorrhage, prolonged bleeding after dental/surgical procedures, GI bleeding

-Dx: decreased vWF, ristocetin cofactor activity, and factor VIII activity. Prolonged PTT, normal PT, and prolonged bleeding time

-Tx: desmopressin

DDVAP

What is the treatment of choice for von Willebrand Deficiency?

G6PD Deficiency

Most common enzyme deficiency worldwide, which allows oxidative stress to denature hemoglobin (Heinz Bodies) and damage the RBC membrane (bite cells). This causes episodic hemolytic anemia. X-linked recessive

-Triggers: infections, sulfonamides, antimalarials, nitrofurantoin, fava beans, DKA

-Presentation: sudden jaundice, pallor, dark urine, back pain, fatigue

-Dx: bite cells and Heinz bodies on peripheral smear, confirmed by G6PD enzyme activity assay

-Tx: supportive care, avoid triggers

ALL

Most common childhood malignancy, with a peak age of 2-5 years

-Presentation: LAD + bone pain + bleeding + fever in a child

-Dx: marrow is > 20% lymphoblasts

-Tx: chemotherapy + CNS prophylaxis (intrathecal methotrexate), TK inhibitors if Ph+

AML

Common blood cancer in adults, which is due to marrow failure

-Presentation: anemia, thrombocytopenia, neutropenia, gum hypertrophy, leukostasis

-Dx: marrow > 20% myeloblasts, Auer rods on smear

-Tx: chemotherapy

CLL

Most common leukemia in adults in the Western world, with a median age of > 70 years old

-Presentation: fatigue, LAD, splenomegaly

-Dx: smudge cells, mature lymphocytes

-Tx: BTK inhibitors

CML

Leukemia seen in adults > 50 years old, which is often found incidentally with marked leukocytosis

-Philadelphia chromosome → t(9;22)

-Presentation: splenomegaly, fatigue, weight loss, night sweats

-Tx: tyrosine kinase inhibitors

Hodgkin Lymphoma

Malignant neoplasm of lymphoid tissue with a bimodal age distribution

-Cells: Reed-Sternberg cells (Owl-eye)

-Spread: contiguous nodal spread, often upper body

-Presentation: fever, drenching night sweats, weight loss

-Related to Epstein Barr Virus

-Prognosis: highly curable

-Tx: ABVD chemotherapy + radiation

Non-Hodgkin Lymphoma

Malignant neoplasm of lymphoid tissue that is more common in elderly patients or those who are immunocompromised

-Cell type: B-cells

-Spread: non-contiguous, extranodal involvement common

-Tx: R-CHOP for aggressive B-cell

Multiple Myeloma

Malignant clonal proliferation of plasma cells in the bone marrow producing a monoclonal immunoglobulin (M-protein), which is the most common primary bone malignancy in adults

-More common in elderly black patients

-Presentation: elevated calcium, renal failure, anemia, bone lesions (lytic and “punched out”)

-Dx: Rouleaux formation on smear, high ESR, elevated globulin gap, M-protein

-Tx: refer to hem/onc

Polycythemia Vera

A myeloproliferative neoplasm with autonomous RBC production, which is related to the JAK2 mutation

-Presentation: hypervolemia, mast-cell-related pruritus, thrombosis, hyperuricemia, eythromelalgia, plethora, headache, splenomegaly, Budd-Chiari syndrome, itching after hot showers

-Dx: EPO low, JAK2 mutation testing

-Tx: therapeutic phlebotomy to maintain hematocrit < 45%

Sickle Cell Disease

Autosomal recessive hemoglobinopathy caused by a point mutation in the B-globin gene, producing HbS that causes rigid sickle cell formation and vaso-occlusion/chronic hemolytic anemia

-Manifestations: vaso-occlusive crises, dactylitis, acute chest syndrome, stroke, aplastic crisis, splenic sequestration, priapism, avascular necrosis

-Dx: hemoglobin electrophoresis, sickled RBCs on smear, Howell-Jolly bodies, target cells, nucleated RBCs, high reticulocyte count

-Tx: hydroxyurea, gene therapy, opioid analgesia for pain crisis, exchange transfusion for acute chest syndrome, and PCN V prophylaxis due to functional asplenia

Alpha Thalassemia

Inherited disorders of globin chain synthesis causing microcytic, hypochromic anemia with ineffective erythropoiesis and varying degrees of hemolysis that is most common in Southeast Asian, Chinese, African, and Mediterranean populations

-Presentation: silent carrier (normal clinically), trait (mild microcytic anemia), hemoglobin H disease (moderate to severe hemolytic anemia, splenomegaly HbH on electrophoresis), and hemoglobin bart hydrops fetalis (incompatible with life)

Beta Thalassemia

Inherited disorders of globin chain synthesis causing microcytic, hypochromic anemia with ineffective erythropoiesis and varying degrees of hemolysis that is most common in Mediterranean, Middle Eastern, and South Asian populations

-Presentation: minor (elevated HbA2), intermedia (moderate symptoms), major (failure to thrive / hepatosplenomegaly / skeletal deformities)

-Transfusion dependent