Differentials

Trauma

History
Exam
1st investigation
Other investigations

history of trauma (including gunshot wounds, major fractures, crush injuries); history of prior bleeding episodes; or use of anticoagulants or non-steroidal anti-inflammatory drug (NSAIDs)

evidence of injury (wounds, bruises, deformities), hypotension, pallor, tachycardia, dyspnea/air hunger, altered mental status or confusion; flat neck veins when supine indicate at least 30% to 40% total body volume loss

  • CBC:

    normal or decreased Hct; decreased Hb; reactive leukocytosis and thrombocytosis due to a stress response, thrombocytopenia from dilutional effect of multiple transfusions

  • reticulocyte count:

    >2%

  • prothrombin time/activated partial thromboplastin time:

    usually normal; prolonged with anticoagulants, underlying defects in hemostasis, or consumptive coagulopathy

    More
  • joint or spine x-rays:

    identification of fractures

  • diagnostic laparotomy:

    identification of bleeding source

  • CT scan of affected body region:

    identification of internal injuries

Acute gastrointestinal (GI) bleeding

History
Exam
1st investigation
Other investigations

history of prior episodes of GI bleeding, gastritis, nonsteroidal anti-inflammatory drug (NSAID) or corticosteroid use, alcohol use, cirrhosis, anticoagulants; rectal bleeding, melena, hematemesis, abdominal pain

hypotension, pallor, tachycardia, dyspnea/air hunger, altered mental status or confusion; flat neck veins when supine indicate at least 30% to 40% total blood volume loss; ascites, hepatomegaly/splenomegaly, cirrhotic hard liver, caput medusae, gynecomastia, melena, or bright red blood on rectal examination

  • CBC:

    normal or decreased Hct; decreased Hb; reactive leukocytosis and thrombocytosis due to a stress response

  • reticulocyte count:

    >2%

  • prothrombin time (PTT)/activated partial thromboplastin time:

    usually normal; prolonged in cirrhosis, anticoagulant therapy, or underlying defects in hemostasis; elevated BUN may be seen

  • upper GI endoscopy:

    bleeding varices or ulcers if source is from upper GI tract

  • colonoscopy:

    visualization of bleeding lesion or mass

Rupture of a vascular aneurysm

History
Exam
1st investigation
Other investigations

may be sudden tearing pain, may be accompanied by loss of consciousness if major vessel involved; history of hypertension, collagen disorders, trauma, cocaine or amphetamine use

hypotension, pallor, tachycardia, dyspnea/air hunger, altered mental status or confusion; flat neck veins when supine indicate at least 30% to 40% total blood volume loss; wide pulse pressure or absent distal pulses; may rapidly progress to circulatory collapse and death

  • CBC:

    normal or decreased Hct; decreased Hb; reactive leukocytosis and thrombocytosis due to a stress response

  • reticulocyte count:

    >2%

  • ultrasonography of affected region:

    shows extent and nature of aneurysm

    More
  • CT scan of affected region:

    shows extent and nature of aneurysm

    More
  • chest x-ray:

    may show widened mediastinum in thoracic aortic aneurysm

    More

Surgery

History
Exam
1st investigation
Other investigations

recent surgery with at least moderate blood loss; history of bleeding disorders or excessive bruising; use of antibiotics

hypotension, pallor, tachycardia, continuous bleeding from surgical wound, petechiae, purpura; severe bleeding produces dyspnea/air hunger, altered mental status or confusion; flat neck veins when supine indicate at least 30% to 40% total blood volume loss

  • CBC:

    normal or decreased Hct; decreased Hb; reactive leukocytosis and thrombocytosis due to a stress response

  • reticulocyte count:

    >2%

  • ultrasound of affected region:

    shows source and extent of bleeding

  • CT scan of affected region:

    shows source and extent of bleeding

  • diagnostic laparotomy:

    shows source and extent of bleeding

Menorrhagia

History
Exam
1st investigation
Other investigations

excessive menstrual bleeding lasting >7 days; fatigue, dyspnea on exertion, pica; use of hormone therapy, history of fibroids

pallor, adnexal masses or fibroids

  • CBC:

    chronic microcytic anemia with normal WBC; reactive thrombocytosis if iron deficient

  • serum ferritin:

    <15 micrograms/L if iron deficient

  • pregnancy test:

    negative

  • prothrombin time/activated partial thromboplastin time:

    usually normal; prolonged with anticoagulants, underlying defects in hemostasis, or consumptive coagulopathy

  • thyroid-stimulating hormone (TSH)/free thyroxine (T4):

    elevated TSH with low free T4 in hypothyroidism

  • transvaginal ultrasound:

    may see hyperplasia, dysplasia, fibroids, or polyps

    More

Iron deficiency

History
Exam
1st investigation
Other investigations

history of poor dietary iron intake, celiac disease, Crohn disease, ulcerative colitis, small bowel resection, peptic ulcer disease, regular running, chronic blood loss (melena, hematuria, menorrhagia, hemoptysis, frequent blood donation, self-harm), pica, salicylate ingestion, gastric bypass, hookworm infestation, pregnancy, or menorrhagia

pallor, dyspnea, poor exercise tolerance, koilonychia, angular cheilosis, glossitis, thinning hair, systolic flow murmur; hemorrhoids, fresh blood or melena on rectal examination; evidence of pregnancy; adnexal masses or fibroids

  • CBC with peripheral smear:

    microcytic anemia with thrombocytosis

  • serum iron studies:

    low serum iron, elevated total iron-binding capacity, low ferritin, elevated soluble transferrin receptor

  • immunoglobulin A-tissue transglutaminase (IgA-tTG) test:

    positive in celiac disease

  • fecal occult blood:

    positive if GI bleeding

  • upper GI endoscopy:

    identification of source of upper GI bleeding; elevated gastric pH in achlorhydria

  • colonoscopy:

    identification of source of lower GI bleeding or chronic inflammation

  • flow cytometry:

    identification of paroxysmal nocturnal hemoglobinuria

  • transvaginal ultrasound:

    may see hyperplasia, dysplasia, fibroids, or polyps

    More
  • stool microscopy:

    visualization of hookworm, whipworm, or Schistosoma eggs

  • Helicobacter pylori test:

    positive result if H pylori  present

    More

Vitamin B12 deficiency

History
Exam
1st investigation
Other investigations

history of celiac or Crohn disease, autoimmune thyroid disease, gastric bypass, chronic antibiotic use (intestinal bacterial overgrowth syndrome), vegan diet or alcohol abuse; fatigue, palpitations, distal paresthesias, depression, confusion, tinnitus, dementia

impaired vibration sense and extremity numbness, vitiligo, glossitis, poor balance or coordination, tachycardia, pallor, hepatosplenomegaly

  • CBC with peripheral smear:

    megaloblastic macrocytic anemia; basophilic stippling may be seen

  • serum vitamin B12 levels:

    low

  • serum methylmalonic acid levels:

    elevated

    More
  • anti-intrinsic factor antibodies:

    positive in pernicious anemia

  • antiparietal cell antibodies:

    positive in pernicious anemia

Folate deficiency

History
Exam
1st investigation
Other investigations

history of celiac or Crohn disease, gastric bypass, hemodialysis, pregnancy, alcohol abuse, or use of antiseizure medications; fatigue, palpitations, headaches

mild persistent pyrexia, tachycardia, pallor, hepatosplenomegaly, glossitis, angular stomatitis, patchy hyperpigmentation of skin and mucous membranes

  • CBC with peripheral smear:

    megaloblastic macrocytic anemia; basophilic stippling may be seen

  • serum folate:

    low

  • serum vitamin B12 levels:

    normal; low in combined vitamin B12 and folate deficiency

    More
  • serum homocysteine levels:

    elevated

Myelodysplastic syndrome

History
Exam
1st investigation
Other investigations

history of prior exposure to petroleum distillates (especially benzene), chemotherapy, or radiation therapy; fever, chills, fatigue, weakness, recurrent infection, anorexia, night sweats, shortness of breath, easy bruising

pallor, petechiae, purpura

  • CBC:

    macrocytic anemia with leukopenia, macro-ovalocytes; associated cytopenias include neutropenia and thrombocytopenia

  • bone marrow aspiration and biopsy:

    myeloblasts with immature precursors

  • cytogenetics of bone marrow biopsy:

    multiple chromosomal translocations possible, especially 5q-, 7q-, or trisomy 8 (+8)

Acute lymphocytic leukemia

History
Exam
1st investigation
Other investigations

malaise, fatigue, easy bruising or bleeding, recurrent infections, fever, arthralgias, infection, anorexia, night sweats, shortness of breath, bony tenderness, epistaxis, bleeding gums, gingival hyperplasia

pallor, petechiae, purpura, tachycardia, hepatosplenomegaly, lymphadenopathy, painless scrotal enlargement, bleeding gums

  • CBC with peripheral smear:

    pancytopenia, with ≥20% blasts; normocytic anemia; may see hypereosinophilia

    More
  • reticulocyte count:

    <2%

  • bone marrow aspirate and biopsy:

    ≥20% blasts

    More

Acute myelogenous leukemia

History
Exam
1st investigation
Other investigations

history of prior chemotherapy or radiation therapy; malaise, night sweats, fatigue, easy bruising or bleeding, recurrent infections, fever, bony tenderness, epistaxis, bleeding gums, gingival hyperplasia

pallor, petechia, purpura, dyspnea, tachycardia

  • CBC with peripheral smear:

    pancytopenia, with ≥20% blasts; normocytic anemia; may see hypereosinophilia

    More
  • reticulocyte count:

    <2%

  • bone marrow aspirate and biopsy:

    ≥20% blasts

    More

Chronic myelogenous leukemia

History
Exam
1st investigation
Other investigations

usually in middle-aged patients; fatigue, weight loss, night sweats, early satiety, petechiae, purpura, recurrent fevers, bone pain, gouty arthritis

tender splenomegaly, painful sternum, lymphadenopathy, splenomegaly

  • CBC with peripheral smear:

    normocytic anemia; myeloid maturing cells, elevated basophils, and eosinophils

  • reticulocyte count:

    <2%

  • bone marrow aspirate and biopsy:

    hypercellular with granulocytic hyperplasia

  • cytogenetics:

    t(19;22) Philadelphia chromosome - bcr-abl translocation

  • serum uric acid:

    elevated

    More

Hairy cell leukemia

History
Exam
1st investigation
Other investigations

weakness, fatigue, weight loss, night sweats, early satiety, petechiae, purpura, recurrent fevers, abdominal discomfort or fullness due to large spleen

massive splenomegaly

  • CBC with peripheral smear:

    pancytopenia with normocytic anemia

    More
  • reticulocyte count:

    <2%

  • bone marrow aspirate and biopsy:

    core biopsy shows hairy cells

    More

Acquired aplastic anemia

History
Exam
1st investigation
Other investigations

history of hepatitis, HIV, benzene exposure, use of known causative medications, radiation exposure, paroxysmal nocturnal hemoglobinuria; malaise, fatigue, easy bruising or bleeding, recurrent infections, fever

pallor, petechiae, purpura, dyspnea, tachycardia

  • CBC with peripheral smear:

    pancytopenia with mild macrocytosis; normocytic anemia

  • reticulocyte count:

    <2%

  • bone marrow aspirate and biopsy:

    hypocellular with decrease in all elements, replaced mostly by fat cells; no infiltration by fibrosis or malignant cells

  • serum vitamin B12:

    normal

  • folate:

    normal

Infiltration by secondary malignancy

History
Exam
1st investigation
Other investigations

weight loss, malaise, fevers, fatigue, dyspnea, easy bleeding or bruising

pallor, petechiae, purpura, tachycardia, abnormal lung exam (if lung cancer), breast mass (if breast cancer), bruising, cachexia

  • CBC with peripheral smear:

    pancytopenia, teardrop cells, poikilocytes; normocytic anemia

  • reticulocyte count:

    <2%

  • bone marrow aspirate and biopsy:

    infiltration of marrow space by malignant cells

    More

Pure red cell aplasia

History
Exam
1st investigation
Other investigations

self-limited disease: history of use of known causative medications, clinical features of causative infections (parvovirus B19, infectious mononucleosis, viral hepatitis, malaria, respiratory infections, gastroenteritis, primary atypical pneumonia, mumps); chronic disease: history of autoimmune disease (systemic lupus erythematosus [SLE], rheumatoid arthritis, dermatomyositis, scleroderma, polyarteritis nodosa), persistent infection, or thymoma

clinical signs of underlying infection or autoimmune disease

  • CBC:

    normocytic anemia

  • reticulocyte count:

    <2%

  • trial of discontinuation of causative medication:

    anemia resolves

  • antiparvovirus B19 antibodies:

    positive in parvovirus infection

    More
  • thick and thin peripheral smear:

    intracellular parasites seen with Wright or Giemsa staining in malaria infection

  • serum IgM + IgG anti-HAV:

    positive in hepatitis A infection

  • serum IgM + IgG HBcAb:

    positive in hepatitis B infection

  • serum HBsAg:

    positive in hepatitis B infection

  • serum IgM + IgG anti-HCV:

    positive in hepatitis C infection

  • antinuclear antibodies:

    positive in SLE or scleroderma

  • ds-DNA, Smith antigen:

    positive in SLE

  • rheumatoid factor:

    positive in rheumatoid arthritis

  • serum creatine kinase (CK):

    elevated in dermatomyositis

  • chest x-ray:

    infiltrates in atypical pneumonia; smooth mass in thymoma, typically projecting into one of the hemithoraces and obscuring the aortic arch, or silhouette sign

Drug toxicity

History
Exam
1st investigation
Other investigations

known or suspected ingestion of causative drug prior to onset of anemia, poor exercise tolerance

pallor, jaundice (with hemolytic anemia only), dyspnea

  • CBC with peripheral smear:

    typically normocytic anemia; inhibitors of DNA synthesis, folate, or vitamin B12 produce megaloblastic macrocytic anemia

  • reticulocyte count:

    <2% if drugs suppress bone marrow; >2% if drugs produce hemolysis

  • trial of discontinuation of causative medication:

    anemia resolves

  • serum bilirubin:

    elevated in hemolytic anemia

Anemia of chronic disease

History
Exam
1st investigation
Other investigations

history of known chronic inflammatory, autoimmune, or infectious states, sustained physiologic stress, renal failure, vasculitis or collagen vascular diseases, poor exercise tolerance; anemia correlates with severity of inflammatory process

pallor, fatigue, dyspnea; specific signs of underlying disease

  • CBC:

    normocytic anemia

    More
  • serum iron studies:

    low/normal serum iron, low total iron-binding capacity and normal/elevated ferritin; ferritin normal or elevated in acute-phase reaction

    More
  • serum erythropoietin level:

    normal or elevated; often decreased in chronic kidney disease

    More

Chronic kidney disease

History
Exam
1st investigation
Other investigations

chronic kidney disease, poor exercise tolerance; features of secondary hypoparathyroidism: muscle cramps, bone pain

pallor, fatigue, dyspnea; signs of renal failure: jaundice, skin bruising, lung rales, pericardial rub, edema, poor concentration or memory, myoclonus; positive Chvostek sign or Trousseau sign in associated hyperparathyroidism

  • CBC:

    normocytic or microcytic anemia with thrombocytosis

  • reticulocyte count:

    <2%

  • serum creatinine:

    elevated

  • urinalysis:

    hematuria and/or proteinuria

  • serum iron studies:

    low serum iron and normal/elevated ferritin, high total iron-binding capacity in iron deficiency

  • serum erythropoietin level:

    normal or decreased

  • serum calcium level:

    decreased in associated secondary hyperparathyroidism

  • serum intact parathyroid hormone level:

    increased in associated secondary hyperparathyroidism

  • renal ultrasound:

    small kidney size; presence of obstruction or hydronephrosis; kidney stones

  • kidney biopsy:

    identification of underlying kidney pathology

Chronic liver disease

History
Exam
1st investigation
Other investigations

history of chronic liver disease, poor exercise tolerance; may be asymptomatic or with fatigue, weakness, weight loss, recurrent infections, decreased libido; altered mental status in hepatic encephalopathy

pallor, fatigue, dyspnea, jaundice, lower-extremity swelling; hand and nail features: leukonychia, palmar erythema, finger clubbing, spider angiomata; facial features: telangiectasia, bruising, rhinophyma, parotid gland swelling, paper-dollar appearance of skin, seborrheic dermatitis, xanthelasma; abdominal features: caput medusae, bruising, hepatomegaly, splenomegaly, abdominal distension; in males, loss of secondary sexual hair and testicular atrophy

  • CBC:

    nonmegaloblastic macrocytic anemia; thrombocytopenia may be present

  • prothrombin time:

    decreased in hepatic synthetic dysfunction

  • liver function tests (LFTs):

    abnormal; pattern depends on underlying cause

  • abdominal ultrasound, CT, or MRI scanning:

    liver surface nodularity, small liver, possible hypertrophy of left/caudate lobe, evidence of ascites or collateral circulation

  • liver biopsy:

    diagnosis of underlying cause or subsequent cirrhosis

Pregnancy

History
Exam
1st investigation
Other investigations

pregnancy, especially in third trimester

abdominal distension consistent with pregnancy

  • CBC:

    microcytic anemia with thrombocytosis in iron deficiency; megaloblastic macrocytic anemia in folate deficiency

  • serum iron studies:

    low serum iron, elevated total iron-binding capacity, low ferritin, elevated soluble transferrin receptor in iron deficiency

  • serum folate:

    low in folate deficiency

Generalized malnutrition

History
Exam
1st investigation
Other investigations

protein calorie deprivation; malabsorption syndrome; neglect; history of an eating disorder

loss of subcutaneous fat, apathy and lethargy, depigmentation, enlarged abdomen, winged scapula, flaky skin, bipedal edema

  • CBC with peripheral smear:

    microcytic anemia in iron deficiency; megaloblastic macrocytic anemia in vitamin B12 and folate deficiency; normocytic anemia with combined vitamin and mineral deficiencies

  • serum iron studies:

    low serum iron, elevated total iron-binding capacity, and low ferritin in iron deficiency

  • serum vitamin B12:

    low

  • serum folate:

    low

  • serum copper level:

    low

    More

Cytotoxic chemotherapy

History
Exam
1st investigation
Other investigations

history of myelosuppressive chemotherapy; fatigue; headaches; poor exercise tolerance

pallor, lethargy, dyspnea

  • CBC:

    pancytopenia with a normocytic anemia

    More
  • reticulocyte count:

    <2%

Radiation therapy

History
Exam
1st investigation
Other investigations

history of recent radiation exposure, especially to pelvic or sternal areas; fatigue, headaches, poor exercise tolerance

pallor, lethargy, dyspnea, skin erythema on radiation sites

  • CBC:

    anemia (pancytopenia)

  • reticulocyte count:

    <2%

Alcohol abuse

History
Exam
1st investigation
Other investigations

history of chronic high alcohol intake

overweight status, increased prominence of superficial cutaneous vasculature, peripheral neuropathy, alterations in normal dentition and halitosis, possible signs of liver disease: hepatomegaly or small liver, jaundice, ascites

  • CBC:

    macrocytic anemia

  • diagnostic interview:

    diagnosis of alcohol dependence

  • alcohol level (breath and blood):

    elevated

Lead toxicity

History
Exam
1st investigation
Other investigations

history of occupational or recreational exposure to lead products or old paint; neuropsychiatric disturbance, insomnia, abdominal pain, poor appetite, pica

blue gingival line (Burton line), hypertension, gout (saturnine gout); wrist or foot drop

  • CBC with peripheral smear:

    normocytic anemia with basophilic stippling; microcytic anemia if associated iron deficiency is present

  • reticulocyte count:

    >2%

  • whole blood lead level:

    elevated

Hypothyroidism

History
Exam
1st investigation
Other investigations

weakness, lethargy, slow speech, feeling cold, forgetfulness, constipation, weight gain, poor exercise tolerance

pallor; dyspnea; coarse, dry skin; eyelid edema; thick tongue; facial edema; bradycardia

  • CBC:

    nonmegaloblastic macrocytic anemia

  • serum TSH:

    elevated

  • serum T4:

    reduced

Autoimmune hemolytic anemia (AIHA)

History
Exam
1st investigation
Other investigations

history of autoimmune diseases (SLE, rheumatoid arthritis, or scleroderma), lymphoproliferative disorders (non-Hodgkin lymphoma or chronic lymphocytic leukemia), recent viral illness, or mononucleosis; may be asymptomatic; symptoms include weakness, fatigue, headaches, poor exercise tolerance, prior gallstones, dark urine, clay-colored stools

pallor, lethargy, dyspnea, tachycardia, jaundice, splenomegaly (especially if extravascular hemolysis)

  • CBC with peripheral smear:

    normocytic anemia, with spherocytes

  • reticulocyte count:

    >2%; usually 4%

    More
  • lactate dehydrogenase (LDH):

    elevated

  • haptoglobin:

    low

  • direct antiglobulin (Coombs) test:

    usually positive; negative in 5% to 10% of cases

  • serum bilirubin:

    elevated

Transfusion reaction

History
Exam
1st investigation
Other investigations

multiple prior transfusions; fever, back pain, and dyspnea, usually within 6 hours of transfusion

pallor, lethargy, dyspnea, dark urine, jaundice

  • ABO typing:

    discrepancy to blood used for transfusion

    More
  • inspection of plasma in centrifuged, anticoagulated venous blood sample:

    clear or pink-red within first few hours of hemoglobinemia

  • inspection of centrifuged urine:

    clear red in hemoglobinemia

  • direct antiglobulin (Coombs) test:

    IgG anti-A, anti-B, or anti-AB detected on circulating red cells

  • serum bilirubin:

    elevated

Malaria

History
Exam
1st investigation
Other investigations

history of mosquito bite or habitation in malaria-prone region; fatigue, dyspnea, fevers and prostration, decreased exercise tolerance, headaches, malaise; symptoms usually cycle every 48 to 72 hours, coinciding with RBC destruction

jaundice or pallor, splenomegaly, dyspnea, high flow cardiac murmur, pulmonary edema, dark urine, fevers

  • CBC:

    normocytic anemia ± thrombocytopenia and leukopenia

  • reticulocyte count:

    >2%; usually 4%

  • thick and thin peripheral smear:

    intracellular parasites seen with Wright or Giemsa staining

    More
  • serum bilirubin:

    elevated

Viral hepatitis

History
Exam
1st investigation
Other investigations

perinatal exposure, direct body fluid transmission, exposure to foodborne outbreak (in hepatitis A); nausea, vomiting, abdominal pain, fever, malaise, fatigue and headache, dark urine, acholic (clay-colored) stools, jaundice, pruritus (in hepatitis B); hepatitis C is usually asymptomatic

jaundice, hepatomegaly, RUQ pain, acholic stools, maculopapular or urticarial skin rash (in hepatitis B); usually normal in hepatitis C

  • CBC:

    normocytic anemia

  • reticulocyte count:

    <2%

  • serum aminotransferases:

    elevated

  • serum IgM + IgG anti-HAV:

    positive in hepatitis A infection

  • serum IgM + IgG HBcAb:

    positive in hepatitis B infection

  • serum HBsAg:

    positive in hepatitis B infection

  • serum IgM + IgG anti-HCV:

    positive in hepatitis C infection

Toxoplasmosis

History
Exam
1st investigation
Other investigations

usually seen in pregnant or immunosuppressed patients and newborns; history of exposure to domestic cats, sheep, or cattle, or to raw meat

jaundice, fever, fatigue, lethargy, rash, hepatosplenomegaly; newborns infected in utero may have chorioretinitis, microcephaly, seizures, mental retardation

  • CBC:

    normocytic anemia and thrombocytopenia; may see leukocytosis and eosinophilia

  • reticulocyte count:

    >2%; usually 4%

  • double-sandwich IgM enzyme-linked immunosorbent assay (ELISA) or IgG avidity test:

    IgM detected in acute infection; IgG detected in chronic or previous exposure

    More
  • Sabin-Feldman dye test:

    IgG antibodies positive

  • PCR for Toxoplasma gondii:

    positive

Leishmaniasis

History
Exam
1st investigation
Other investigations

history of exposure to sand fly bite, especially in tropical or subtropical zones; AIDS, immunosuppression, or malnutrition; fatigue and anorexia; prolonged, persistent, low-grade intermittent fevers; failure to thrive, distended abdomen

pallor, jaundice, hepatosplenomegaly, lymphadenopathy, diarrhea, skin ulcerations, nasopharyngeal ulcerations

  • CBC:

    normocytic anemia, thrombocytopenia, leukopenia, erythroblastosis

  • reticulocyte count:

    >2%

  • splenic or bone marrow aspirate:

    presence of amastigotes of the parasite

    More
  • direct antiglobulin (Coombs) test:

    positive

Parvovirus B19 infection

History
Exam
1st investigation
Other investigations

acute infection: characteristic skin rash with or without arthralgia

acute infection: "slapped cheek" appearance followed by a reticular erythematous eruption on extremities, and arthritis of hands, wrists, knees, or ankles

  • CBC:

    normocytic anemia

  • reticulocyte count:

    <2%

  • antiparvovirus B19 antibodies:

    positive

    More

Infectious mononucleosis

History
Exam
1st investigation
Other investigations

fatigue, malaise, sore throat, nausea, ocular pain, photophobia

fever, lymphadenopathy, pharyngitis, rash, tender splenomegaly, palate petechiae, periorbital edema, jaundice

  • CBC with peripheral smear:

    normocytic anemia, with spherocytes and atypical lymphocytes

  • reticulocyte count:

    >2% and usually 4% in hemolytic anemia, <2% in pure red cell aplasia

  • lactate dehydrogenase (LDH):

    elevated

  • haptoglobin:

    low

  • monospot test or Epstein-Barr virus (EBV) IgM:

    positive

Cytomegalovirus (CMV)

History
Exam
1st investigation
Other investigations

infection is usually asymptomatic; a maculopapular rash following administration of antibiotics may occur; fatigue occurs due to anemia; symptomatic infection is a sign of underlying immunosuppression

usually normal; jaundice occurs due to hemolytic anemia; symptomatic infection produces fever, lymphadenopathy, pharyngitis, rash, tender splenomegaly, palate petechiae, periorbital edema

  • CBC:

    normocytic anemia

  • reticulocyte count:

    >2%; usually 4%

  • lactate dehydrogenase (LDH):

    elevated

  • haptoglobin:

    low

  • monospot test or Epstein-Barr virus (EBV) IgM:

    negative

    More
  • CMV IgM:

    positive

Sickle cell anemia

History
Exam
1st investigation
Other investigations

known diagnosis of sickle cell disease in patient and/or parents; prior painful vaso-occlusive crises; fatigue, poor exercise tolerance; persistent pain in skeleton, chest, or abdomen; priapism, gallstones, stroke, lower-extremity skin ulcers, pneumonia-like syndrome

high fever, pallor, lethargy, dyspnea, jaundice during acute crisis

  • CBC with peripheral smear:

    normocytic anemia with sickle cells

    More
  • reticulocyte count:

    >2%

  • hemoglobin (Hb) isoelectric focusing:

    elevated HbS/A ratio (close to 100/0)

  • LDH:

    elevated

  • serum bilirubin:

    elevated

Thalassemias

History
Exam
1st investigation
Other investigations

family history of blood disorders, especially requiring repeated transfusions; Mediterranean, Middle Eastern, or Southeast Asian descent; variable severity ranging from asymptomatic to severe transfusion-dependent symptoms

splenomegaly, jaundice, abdominal distension, icterus; skeletal abnormalities, large head, chipmunk facies, and misaligned teeth seen in beta-thalassemia intermedia and major

  • CBC with peripheral smear:

    microcytic anemia with mean corpuscular volume (MCV) typically closer to 70 fL, low mean corpuscular hemoglobin (Hb); target cells seen

  • Hb electrophoresis:

    elevated HbF; other Hb patterns consistent with respective thalassemias

  • serum ferritin:

    elevated in iron overload

Hereditary spherocytosis

History
Exam
1st investigation
Other investigations

family history of blood disorder, splenectomy, or pigmented gallstones; may be asymptomatic if extramedullary hematopoiesis compensates

may be normal or show pallor, jaundice, lower leg skin ulcers, splenomegaly

  • CBC with peripheral smear:

    normocytic anemia, with increased mean corpuscular hemoglobin and spherocytes

  • reticulocyte count:

    >2%

  • osmotic fragility test:

    positive (cells lyse on exposure to hypo-osmotic solution)

  • direct antiglobulin (Coombs) test:

    negative

    More

Glucose-6-phosphate dehydrogenase deficiency (G6PD)

History
Exam
1st investigation
Other investigations

usually in males of African, Mediterranean, Sardinian, or Sephardic Jewish descent; self-limited episodes of acute hemolysis when exposed to oxidant stress; life-threatening symptoms more common with Mediterranean variant

pallor, jaundice, mild dyspnea

  • CBC with peripheral smear:

    normocytic anemia with Heinz bodies, eccentrocytes, or bite cells

    More
  • reticulocyte count:

    >2%

  • serum haptoglobin:

    decreased

  • lactate dehydrogenase (LDH):

    elevated

  • G6PD enzyme assays:

    quantitative or qualitative abnormalities

    More
  • serum bilirubin:

    elevated indirect bilirubin

  • direct antiglobulin (Coombs) test:

    negative

    More

Bone marrow failure syndromes

History
Exam
1st investigation
Other investigations

recurrent infection shortly after birth, fever, easy bleeding or bruising, organ abnormalities, short stature

ill-appearing, with weight loss, pallor, lethargy, dyspnea, petechiae, purpura, and/or thrush

  • CBC with peripheral smear:

    pancytopenia with normocytic or macrocytic anemia

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  • reticulocyte count:

    <2%

  • bone marrow aspiration and biopsy:

    varies depending on underlying cause

  • diepoxybutane or mitomycin-c fragility test:

    positive in Fanconi anemia

  • genetic testing:

    characteristic genetic mutations detected

Hemolytic uremic syndrome

History
Exam
1st investigation
Other investigations

acute renal failure usually following an enteric bacterial infection ( Escherichia coli 0157:H7) with bloody diarrhea, or Streptococcus pneumoniae

pallor, lethargy, dyspnea, petechiae, purpura, bloody diarrhea; usually self-limited in children

  • CBC with peripheral smear:

    normocytic anemia, thrombocytopenia, schistocytes

  • erythrocyte count:

    >2%

  • prothrombin time/activated partial thromboplastin time:

    normal

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  • serum haptoglobin:

    decreased

  • lactate dehydrogenase (LDH):

    elevated

  • serum bilirubin:

    elevated

  • direct antiglobulin (Coombs) test:

    negative

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  • kidney biopsy:

    hyaline arteriolar thrombi in absence of inflammatory changes in vessel wall

Disseminated intravascular coagulation (DIC)

History
Exam
1st investigation
Other investigations

ongoing severe infection, sepsis (typically gram-negative), malignancy, obstetric emergency, trauma, burns, envenomations, drug overdose, any cause of endothelial damage

diffuse bleeding, especially from puncture sites or minor trauma; unprovoked clots; clinical signs of underlying cause

  • CBC with peripheral smear:

    normocytic anemia, thrombocytopenia, schistocytes

  • prothrombin time:

    prolonged

  • activated partial thromboplastin time:

    varies depending on factor VII levels

  • DIC panel:

    elevated D-dimer and fibrin degradation products with low fibrinogen

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Thrombotic thrombocytopenic purpura

History
Exam
1st investigation
Other investigations

nonspecific prodrome followed by headache, confusion, focal weakness, seizures, coma; menorrhagia may be seen due to bleeding

pallor, lethargy, dyspnea, purpura, ecchymoses

  • CBC with peripheral smear:

    normocytic anemia with schistocytes

  • reticulocyte count:

    >2%

  • direct antiglobulin (Coombs) test:

    negative

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Hemangioma

History
Exam
1st investigation
Other investigations

typically young child or infant with expanding vascular skin lesion; may also be hepatic or in other visceral site

depends on location of lesion(s), which are typically reddish-brown or violaceous; other symptoms consistent with anemia

  • CBC with peripheral smear:

    normocytic anemia, thrombocytopenia

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  • reticulocyte count:

    >2%

  • x-ray of suspected region:

    soft-tissue shadows, phleboliths

  • MRI of suspected region:

    increased signal on both T1- and T2-weighted images with areas of signal void

Malignant hypertension

History
Exam
1st investigation
Other investigations

history of essential hypertension, renal disease, or eclampsia; older age, male gender, black ethnicity; dizziness, headache, mental status changes, loss of sensation or motor strength, chest pain or pressure, dyspnea, edema

systolic BP >210 mmHg and diastolic BP >130 mmHg, lethargy, new murmurs, S3 on auscultation of heart, jugular venous distension, rales or lower-extremity edema, oliguria or polyuria, focal neurologic signs, hypertensive retinopathy

  • CBC with peripheral smear:

    normocytic anemia with schistocytes

  • reticulocyte count:

    >2%

  • ECG:

    evidence of ischemia or infarct such as ST- or T-wave changes

  • serum creatinine:

    elevated with renal failure

  • chest x-ray:

    evidence of pulmonary edema indicating left ventricular failure

  • head CT or MRI:

    evidence of infarct or hemorrhage

Prosthetic valves and surfaces

History
Exam
1st investigation
Other investigations

history of aortic or mitral metallic valve replacement, with anticoagulation; weakness, fatigue, headaches; poor exercise tolerance, prior gallstones, dark urine

pallor, lethargy, dyspnea, petechiae, purpura, jaundice

  • CBC with peripheral smear:

    normocytic anemia with schistocytes

  • reticulocyte count:

    >2%

  • direct antiglobulin (Coombs) test:

    negative

    More

Cutaneous burns

History
Exam
1st investigation
Other investigations

burn injury to at least 10% of total body surface area (TBSA); multiple surgical procedures

epidermal or dermal loss consistent with burn injury

  • CBC with peripheral smear:

    normocytic anemia with thrombocytopenia; schistocytes from peripheral destruction seen on blood smear

  • reticulocyte count:

    >2%

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