Differentials

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 drugs (NSAIDs)

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

  • FBC:

    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 haemostasis, 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

History
Exam
1st investigation
Other investigations

history of prior episodes of GI bleeding, gastritis, peptic ulcer disease, hiatal hernia, neoplastic disease, non-steroidal anti-inflammatory drug (NSAID) or corticosteroid use, alcohol use, cirrhosis, anticoagulants, ulcerative colitis, diverticulosis; symptoms of rectal bleeding, melaena, haematemesis, abdominal pain

hypotension, pallor, tachycardia, dyspnoea/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, gynaecomastia, melaena, or bright red blood on rectal examination

  • FBC:

    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 haemostasis; elevated urea may be seen

  • upper GI endoscopy:

    bleeding varices or ulcers if source is from upper GI tract

  • colonoscopy:

    visualisation of bleeding lesion or mass

    History
    Exam
    1st investigation
    Other investigations

    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, dyspnoea/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

    • FBC:

      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
    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 dyspnoea/air hunger, altered mental status or confusion; flat neck veins when supine indicate at least 30% to 40% total blood volume loss

    • FBC:

      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

    History
    Exam
    1st investigation
    Other investigations

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

    pallor, adnexal masses or fibroids

    • FBC:

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

    • serum ferritin:

      <33 picomol/L (<15 micrograms/L) if iron deficient

    • pregnancy test:

      negative

    • prothrombin time/activated partial thromboplastin time:

      usually normal; prolonged with anticoagulants, underlying defects in haemostasis, 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
    History
    Exam
    1st investigation
    Other investigations

    history of poor dietary iron intake, coeliac disease, Crohn's disease, ulcerative colitis, small bowel resection, peptic ulcer disease, regular running, chronic blood loss (melaena, haematuria, menorrhagia, haemoptysis, frequent blood donation, self-harm), pica, salicylate ingestion, gastric bypass, hookworm infestation, pregnancy, or menorrhagia

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

    • FBC with peripheral smear:

      microcytic anaemia 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 coeliac disease

    • 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

    • CT colonography:

      Identification of source of lower GI bleeding

      More
    • flow cytometry:

      identification of paroxysmal nocturnal haemoglobinuria

    • transvaginal ultrasound:

      may see hyperplasia, dysplasia, fibroids, or polyps

      More
    • stool microscopy:

      visualisation of hookworm, whipworm, or Schistosoma eggs

    • Helicobacter pylori test:

      positive result if H pylori present

      More
    History
    Exam
    1st investigation
    Other investigations

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

    impaired vibration sense and extremity numbness, vitiligo, glossitis, poor balance or co-ordination, tachycardia, pallor, hepatosplenomegaly

    • FBC with peripheral smear:

      megaloblastic macrocytic anaemia; basophilic stippling may be seen

    • serum vitamin B12 levels:

      low

    • serum methylmalonic acid levels:

      elevated

      More
    • anti-intrinsic factor antibodies:

      positive in pernicious anaemia

    • antiparietal cell antibodies:

      positive in pernicious anaemia

      History
      Exam
      1st investigation
      Other investigations

      history of coeliac or Crohn's disease, gastric bypass, haemodialysis, pregnancy, alcohol abuse, or use of anti-seizure medications; fatigue, palpitations, headaches

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

      • FBC with peripheral smear:

        megaloblastic macrocytic anaemia; 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

      History
      Exam
      1st investigation
      Other investigations

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

      pallor, petechiae, purpura

      • FBC:

        macrocytic anaemia 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)

      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

      • FBC with peripheral smear:

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

        More
      • reticulocyte count:

        <2%

      • bone marrow aspirate and biopsy:

        ≥20% blasts

        More
      History
      Exam
      1st investigation
      Other investigations

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

      pallor, petechia, purpura, dyspnoea, tachycardia

      • FBC with peripheral smear:

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

        More
      • reticulocyte count:

        <2%

      • bone marrow aspirate and biopsy:

        ≥20% blasts

        More
      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

      • FBC with peripheral smear:

        normocytic anaemia; 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
      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

      • FBC with peripheral smear:

        pancytopenia with normocytic anaemia

        More
      • reticulocyte count:

        <2%

      • bone marrow aspirate and biopsy:

        core biopsy shows hairy cells

        More
      History
      Exam
      1st investigation
      Other investigations

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

      pallor, petechiae, purpura, dyspnoea, tachycardia

      • FBC with peripheral smear:

        pancytopenia with mild macrocytosis; normocytic anaemia

      • 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

      History
      Exam
      1st investigation
      Other investigations

      weight loss, malaise, fevers, fatigue, dyspnoea, easy bleeding or bruising; history of solid organ malignancy (particularly breast, prostate, lung, neuroblastoma)

      pallor, petechiae, purpura, tachycardia, abnormal exam or presence of mass (if solid organ malignancy), bruising, cachexia

      • FBC with peripheral smear:

        pancytopenia, teardrop cells, poikilocytes; normocytic anaemia

      • reticulocyte count:

        <2%

      • bone marrow aspirate and biopsy:

        infiltration of marrow space by malignant cells

        More
      • CT imaging:

        identification of site of primary malignancy

      History
      Exam
      1st investigation
      Other investigations

      self-limiting 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

      • FBC:

        normocytic anaemia

      • reticulocyte count:

        <2%

      • trial of discontinuation of causative medication:

        anaemia resolves

      • antiparvovirus B19 antibodies:

        positive in parvovirus infection

        More
      • thick and thin peripheral smear:

        intracellular parasites seen with Wright's 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's 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 hemi-thoraces and obscuring the aortic arch, or silhouette sign

      History
      Exam
      1st investigation
      Other investigations

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

      pallor, jaundice (with haemolytic anaemia only), dyspnoea

      • FBC with peripheral smear:

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

      • reticulocyte count:

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

      • trial of discontinuation of causative medication:

        anaemia resolves

      • serum bilirubin:

        elevated in haemolytic anaemia

      History
      Exam
      1st investigation
      Other investigations

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

      pallor, fatigue, dyspnoea; specific signs of underlying disease

      • FBC:

        normocytic anaemia

        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
      History
      Exam
      1st investigation
      Other investigations

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

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

      • FBC:

        normocytic or microcytic anaemia with thrombocytosis

      • reticulocyte count:

        <2%

      • serum creatinine:

        elevated

      • urinalysis:

        haematuria 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

      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, dyspnoea, 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, seborrhoeic dermatitis, xanthelasma; abdominal features: caput medusae, bruising, hepatomegaly, splenomegaly, abdominal distension; in males, loss of secondary sexual hair and testicular atrophy, gynaecomastia

      • FBC:

        non-megaloblastic macrocytic anaemia; 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

      History
      Exam
      1st investigation
      Other investigations

      pregnancy, especially in third trimester

      abdominal distension consistent with pregnancy

      • FBC:

        microcytic anaemia with thrombocytosis in iron deficiency; megaloblastic macrocytic anaemia 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

      Uncommon

      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 oedema

      • FBC with peripheral smear:

        microcytic anaemia in iron deficiency; megaloblastic macrocytic anaemia in vitamin B12 and folate deficiency; normocytic anaemia 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
      History
      Exam
      1st investigation
      Other investigations

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

      pallor, lethargy, dyspnoea

      • FBC:

        pancytopenia with a normocytic anaemia

        More
      • reticulocyte count:

        <2%

        History
        Exam
        1st investigation
        Other investigations

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

        pallor, lethargy, dyspnoea, skin erythema on radiation sites

        • FBC:

          anaemia (pancytopenia)

        • reticulocyte count:

          <2%

        • bone marrow aspirate and biopsy:

          marrow fibrosis or malignant infiltration

        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

        • FBC:

          macrocytic anaemia

        • diagnostic interview:

          diagnosis of alcohol dependence

        • alcohol level (breath and blood):

          elevated

        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's line), hypertension, gout (saturnine gout); wrist or foot drop

        • FBC with peripheral smear:

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

        • reticulocyte count:

          >2%

        • whole blood lead level:

          elevated

          History
          Exam
          1st investigation
          Other investigations

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

          pallor; dyspnoea; coarse, dry skin; eyelid oedema; thick tongue; facial oedema; bradycardia

          • FBC:

            non-megaloblastic macrocytic anaemia

          • serum TSH:

            elevated

          • serum T4:

            reduced

            History
            Exam
            1st investigation
            Other investigations

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

            pallor, lethargy, dyspnoea, tachycardia, jaundice, splenomegaly (especially if extravascular haemolysis)

            • FBC with peripheral smear:

              normocytic anaemia, 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

              History
              Exam
              1st investigation
              Other investigations

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

              pallor, lethargy, dyspnoea, 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 haemoglobinaemia

              • inspection of centrifuged urine:

                clear red in haemoglobinaemia

              • direct antiglobulin (Coombs') test:

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

              • serum bilirubin:

                elevated

              History
              Exam
              1st investigation
              Other investigations

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

              jaundice or pallor, splenomegaly, dyspnoea, high flow cardiac murmur, pulmonary oedema, dark urine, fevers

              • FBC:

                normocytic anaemia ± thrombocytopenia and leukopenia

              • reticulocyte count:

                >2%; usually 4%

              • thick and thin peripheral smear:

                intracellular parasites seen with Wright's or Giemsa staining

                More
              • serum bilirubin:

                elevated

              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-coloured) 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

              • FBC:

                normocytic anaemia

              • 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

                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

                • FBC:

                  normocytic anaemia and thrombocytopenia; may see leukocytosis and eosinophilia

                • reticulocyte count:

                  >2%; usually 4%

                • 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

                History
                Exam
                1st investigation
                Other investigations

                history of exposure to sandfly 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, diarrhoea, skin ulcerations, nasopharyngeal ulcerations

                • FBC:

                  normocytic anaemia, thrombocytopenia, leukopenia, erythroblastosis

                • reticulocyte count:

                  >2%

                • splenic or bone marrow aspirate:

                  presence of amastigotes of the parasite

                  More
                • direct antiglobulin (Coombs') test:

                  positive

                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

                • FBC:

                  normocytic anaemia

                • reticulocyte count:

                  <2%

                • antiparvovirus B19 antibodies:

                  positive

                  More
                History
                Exam
                1st investigation
                Other investigations

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

                fever, lymphadenopathy, pharyngitis, rash, tender splenomegaly, palatal petechiae, periorbital oedema, jaundice

                • FBC with peripheral smear:

                  normocytic anaemia, with spherocytes and atypical lymphocytes

                • reticulocyte count:

                  >2% and usually 4% in haemolytic anaemia, <2% in pure red cell aplasia

                • lactate dehydrogenase (LDH):

                  elevated

                • haptoglobin:

                  low

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

                  positive

                History
                Exam
                1st investigation
                Other investigations

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

                usually normal; jaundice occurs due to haemolytic anaemia; symptomatic infection produces fever, lymphadenopathy, pharyngitis, rash, tender splenomegaly, palatal petechiae, periorbital oedema

                • FBC:

                  normocytic anaemia

                • reticulocyte count:

                  >2%; usually 4%

                • lactate dehydrogenase (LDH):

                  elevated

                • haptoglobin:

                  low

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

                  negative

                  More
                • CMV IgM:

                  positive

                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, dyspnoea, jaundice during acute crisis

                • FBC with peripheral smear:

                  normocytic anaemia with sickle cells

                  More
                • reticulocyte count:

                  >2%

                • haemoglobin (Hb) isoelectric focusing:

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

                • LDH:

                  elevated

                • serum bilirubin:

                  elevated

                  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-thalassaemia intermedia and major

                  • FBC with peripheral smear:

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

                  • Hb electrophoresis:

                    elevated HbF; other Hb patterns consistent with respective thalassaemias

                  • serum ferritin:

                    elevated in iron overload

                  History
                  Exam
                  1st investigation
                  Other investigations

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

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

                  • FBC with peripheral smear:

                    normocytic anaemia, with increased mean corpuscular haemoglobin and spherocytes

                  • reticulocyte count:

                    >2%

                  • osmotic fragility test:

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

                  • direct antiglobulin (Coombs') test:

                    negative

                    More
                  History
                  Exam
                  1st investigation
                  Other investigations

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

                  pallor, jaundice, mild dyspnoea

                  • FBC with peripheral smear:

                    normocytic anaemia 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
                  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, dyspnoea, petechiae, purpura, and/or thrush

                  • FBC with peripheral smear:

                    pancytopenia with normocytic or macrocytic anaemia

                    More
                  • reticulocyte count:

                    <2%

                  • bone marrow aspiration and biopsy:

                    varies depending on underlying cause

                  • diepoxybutane or mitomycin-c fragility test:

                    positive in Fanconi anaemia

                  • genetic testing:

                    characteristic genetic mutations detected

                  History
                  Exam
                  1st investigation
                  Other investigations

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

                  pallor, lethargy, dyspnoea, petechiae, purpura, bloody diarrhoea; usually self-limiting in children

                  • FBC with peripheral smear:

                    normocytic anaemia, thrombocytopenia, schistocytes

                  • erythrocyte count:

                    >2%

                  • prothrombin time/activated partial thromboplastin time:

                    normal

                    More
                  • serum haptoglobin:

                    decreased

                  • lactate dehydrogenase (LDH):

                    elevated

                  • serum bilirubin:

                    elevated

                  • direct antiglobulin (Coombs') test:

                    negative

                    More
                  • kidney biopsy:

                    hyaline arteriolar thrombi in absence of inflammatory changes in vessel wall

                  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

                  • FBC with peripheral smear:

                    normocytic anaemia, 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

                    More
                    History
                    Exam
                    1st investigation
                    Other investigations

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

                    pallor, lethargy, dyspnoea, purpura, ecchymoses

                    • FBC with peripheral smear:

                      normocytic anaemia with schistocytes

                    • reticulocyte count:

                      >2%

                    • direct antiglobulin (Coombs') test:

                      negative

                      More
                      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 anaemia

                      • FBC with peripheral smear:

                        normocytic anaemia, thrombocytopenia

                        More
                      • 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

                      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, dyspnoea, oedema

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

                      • FBC with peripheral smear:

                        normocytic anaemia with schistocytes

                      • reticulocyte count:

                        >2%

                      • ECG:

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

                      • serum creatinine:

                        elevated with renal failure

                      • chest x-ray:

                        evidence of pulmonary oedema indicating left ventricular failure

                      • head CT or MRI:

                        evidence of infarct or haemorrhage

                      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, dyspnoea, petechiae, purpura, jaundice

                      • FBC with peripheral smear:

                        normocytic anaemia with schistocytes

                      • reticulocyte count:

                        >2%

                      • direct antiglobulin (Coombs') test:

                        negative

                        More
                        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

                        • FBC with peripheral smear:

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

                        • reticulocyte count:

                          >2%

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