Differentials

Common

Chemotherapy

History

transient pancytopenia associated with chemotherapeutic agents

Exam

nausea and vomiting, hair loss, easy bruising, bleeding, pallor, fever, rigors

1st investigation
  • peripheral blood:

    irregular size and shape of red blood cells (anisocytosis and poikilocytosis), basophilic stippling

Other investigations
  • bone marrow aspirate:

    variable hypoplasia

    More
  • bone marrow biopsy:

    hypoplasia, megaloblastosis

    More

Radiotherapy

History

transient pancytopenia associated with radiotherapy

Exam

nausea and vomiting, hair loss, easy bruising, bleeding, pallor, fever, rigors

1st investigation
  • peripheral blood:

    irregular size and shape of red blood cells (anisocytosis and poikilocytosis), basophilic stippling

Other investigations
  • bone marrow aspirate:

    variable hypoplasia

    More
  • bone marrow biopsy:

    hypoplasia, megaloblastosis

    More

Vitamin B12 deficiency

History

may be a history of autoimmune disorders, vegan diet, total or partial gastrectomy, ileal resection, or coeliac disease; gradual onset of fatigue

Exam

glossitis and angular stomatitis, easy bruising or spontaneous bleeding (rare), peripheral sensory loss, balance and gait disturbance

1st investigation
  • peripheral blood film:

    oval macrocytic red blood cells (RBCs), irregular size and shape of RBCs (anisocytosis and poikilocytosis), hypersegmented granulocytes (>5 lobes)

    More
  • serum reticulocyte count:

    usually low

  • serum B12:

    low in B12 deficiency

    More
  • bone marrow aspirate:

    hypercellular, megaloblastic erythroblasts, giant metamyelocytes

  • serum LDH:

    moderately raised

  • serum bilirubin:

    moderately raised, mostly indirect

Other investigations
  • intrinsic factor antibody:

    may be positive

    More

Folic acid deficiency

History

may be a history of diet poor in green vegetables, ileal resection, pregnancy with hyperemesis; gradual onset of fatigue

Exam

glossitis and angular stomatitis, easy bruising or spontaneous bleeding (rare), peripheral sensory loss, balance and gait disturbance

1st investigation
  • peripheral blood film:

    oval macrocytic red blood cells (RBCs), irregular size and shape of RBCs (anisocytosis and poikilocytosis), hypersegmented granulocytes (>5 lobes)

    More
  • serum reticulocyte count:

    usually low

  • serum RBC folate:

    low in folate deficiency

  • bone marrow aspirate:

    hypercellular, megaloblastic erythroblasts, giant metamyelocytes

  • serum LDH:

    moderately raised

  • serum bilirubin:

    moderately raised, mostly indirect

Other investigations

    Bone marrow infiltration by non-haematological malignancy

    History

    may be a history of breast, prostate, lung, thyroid, kidney, gastrointestinal malignancy or metastatic melanoma in adults; neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma, retinoblastoma in children; weight loss, anorexia, fatigue

    Exam

    cachexia, finger clubbing, breast lump, lymphadenopathy, enlarged irregular prostate, abdominal mass

    1st investigation
    • peripheral blood film:

      leuko-erythroblastic cell forms

    • bone marrow aspirate:

      clumps of tumour cells

      More
    • chest x-ray:

      mass (lung cancer)

    • serum liver function tests:

      elevated alanine aminotransferase and aspartate aminotransferase (hepatic metastases)

    • serum coagulation profile:

      prolonged prothrombin time and partial thromboplastin time

    • serum fibrinogen and D-dimer:

      diminished fibrinogen and elevated D-dimer (indicative of chronic disseminated intravascular coagulation)

      More
    Other investigations
    • CT of abdomen:

      may reveal abdominal or renal mass

    • serum prostate-specific antigen:

      elevated in prostate cancer

    • thyroid ultrasound:

      irregular mass or nodule

    • breast imaging:

      mass or calcifications

    Non-Hodgkin's lymphoma

    History

    gradual onset of fatigue, weight loss, lymphadenopathy, fever, rigors, respiratory distress, abdominal distention

    Exam

    cachexia, lymphadenopathy, hepatosplenomegaly

    1st investigation
    • peripheral blood film:

      variable; may show circulating lymphoma cells

    • bone marrow aspirate:

      increased proportion of lymphoid cells

    • immunophenotyping (of peripheral blood or bone marrow):

      clonal population of lymphoid cells

    • lymph node biopsy:

      lymphoproliferative disorder

    Other investigations
    • polymerase chain reaction for tumour markers:

      Bcl1 and Bcl2; T-cell receptor

    Hairy cell leukaemia

    History

    gradual onset of fatigue, weight loss, lymphadenopathy, fever, rigors, respiratory distress, abdominal distention

    Exam

    cachexia, lymphadenopathy, hepatosplenomegaly

    1st investigation
    • peripheral blood film:

      presence of hairy cells

      More
    • bone marrow aspirate:

      increased proportion of lymphoid cells

    • immunophenotyping (of peripheral blood or bone marrow):

      clonal population of lymphoid cells

    Other investigations
    • flow cytometry:

      positive for immunophenotypic markers for hairy cell leukaemia

    Chronic lymphocytic leukaemia

    History

    gradual onset of fatigue, weight loss, lymphadenopathy, fever, rigors, respiratory distress, abdominal distention

    Exam

    cachexia, lymphadenopathy, hepatosplenomegaly

    1st investigation
    • peripheral blood film:

      circulating leukaemia cells

    • bone marrow aspirate:

      increased proportion of lymphoid cells

    • immunophenotyping (of peripheral blood or bone marrow):

      clonal population of lymphoid cells

    Other investigations
    • lymph node biopsy:

      lymphoproliferative disorder

    Myelodysplasia

    History

    incidental presentation common, gradual onset of fatigue, shortness of breath, recurrent infection, easy bruising, spontaneous mucosal bleeding, abdominal fullness

    Exam

    pallor, oedema, purpura, or petechiae

    1st investigation
    • peripheral blood film:

      may have irregular or macrocytic red blood cells, dysplastic granulocytes, platelets may be large and hypogranular

    • serum reticulocyte count:

      usually low, may be normal or raised

    • bone marrow aspirate:

      usually hypercellular, rarely, hypocellular (hypocellular myelodysplasia [MDS]), dysplastic changes

    Other investigations
    • cytogenetics:

      may be MDS-associated cytogenetic abnormalities

      More

    Cirrhosis

    History

    liver disease secondary to viral, autoimmune, or alcoholic hepatitis

    Exam

    pallor, jaundiced sclerae, abdominal distension, ascites, hepatosplenomegaly, dilated blood vessels on the face, male breast enlargement, distended blood vessels across the abdomen, atrophy of the testicles, red-coloured palms, white-coloured nails, decreased body hair, muscle cramps, itching, poor sleep, sexual dysfunction

    1st investigation
    • peripheral blood film:

      macrocytes, target cells, stomatocytes, acanthocytes

    • reticulocyte count:

      elevated or normal

    • serum liver function tests:

      may be elevated

    Other investigations
    • bone marrow aspirate:

      hypercellular, erythroid hyperplasia

    Hepatitis B

    History

    key risk factors include living in/travel to an endemic region, intravenous drug use, multiple sexual partners, men who have sex with men, family history of hepatitis B infection or hepatocellular carcinoma, household contact with an infected individual, incarceration

    Exam

    pallor, jaundice, abdominal pain, ascites, hepatosplenomegaly

    1st investigation
    • peripheral blood film:

      macrocytes, target cells, stomatocytes, acanthocytes

    • reticulocyte count:

      elevated or normal

    • serum liver function tests:

      elevated

    • serum hepatitis B surface antigen (HBsAg):

      positive

    Other investigations
    • bone marrow aspirate:

      hypercellular, erythroid hyperplasia

    Hepatitis C

    History

    intravenous drug use or transfusion, fatigue, myalgia, arthralgia

    Exam

    pallor, jaundice, ascites, spider haemangiomata

    1st investigation
    • peripheral blood film:

      macrocytes, target cells, stomatocytes, acanthocytes

    • reticulocyte count:

      elevated or normal

    • serum liver function tests:

      normal or elevated

    • serum hepatitis C virus (HCV) antibody:

      positive

    Other investigations
    • bone marrow aspirate:

      hypercellular, erythroid hyperplasia

    Autoimmune hepatitis

    History

    fatigue, malaise, anorexia, nausea, pruritus

    Exam

    pallor, jaundice, ascites, hepatosplenomegaly, encephalopathy

    1st investigation
    • peripheral blood film:

      macrocytes, target cells, stomatocytes, acanthocytes

    • reticulocyte count:

      elevated or normal

    • serum liver function tests:

      elevated

    • autoantibody screen:

      positive

      More
    Other investigations
    • bone marrow aspirate:

      hypercellular, erythroid hyperplasia

    HIV

    History

    HIV disease or risk factors, influenza-like illness (acute seroconversion), fatigue, easy bruising, spontaneous bleeding, fever, rigors (chronic HIV disease)

    Exam

    cachexia, generalised lymphadenopathy, HIV-associated skin lesions (oral hairy leukoplakia, molluscum contagiosum, Kaposi's sarcoma)

    1st investigation
    • peripheral blood film:

      atypical lymphocytes (acute seroconversion), stacked red blood cells (rouleaux formation), dysplastic neutrophils

    • reticulocyte count:

      reduced

    • HIV serology:

      positive

    • bone marrow aspirate:

      hypercellular (acute seroconversion), hypocellular, dyserythropoiesis

    Other investigations
    • protein electrophoresis:

      polyclonal hypergammaglobulinaemia

    Cytomegalovirus infection

    History

    fever, malaise, arthralgia, tender lymphadenopathy, pharyngitis

    Exam

    fever, generalised tender lymphadenopathy, pharyngeal exudates, mild splenomegaly, abdominal tenderness

    1st investigation
    • peripheral blood film:

      atypical lymphocytes, spherocytes if co-existing haemolysis

    • cytomegalovirus-specific IgM and IgG:

      positive

      More
    • quantitative nucleic acid amplification test:

      number of genomic copies per volume of specimen

    • bone marrow aspirate:

      cellularity usually increased, haemophagocytosis may be prominent

    • bone marrow trephine biopsy:

      cellularity usually increased

    Other investigations

      Mycobacterial infection

      History

      HIV disease or other chronic immunosuppression, fever, weight loss, skin lesions, cough

      Exam

      cachexia, lymphadenopathy

      1st investigation
      • peripheral blood film:

        Stacked red blood cells (rouleaux formation)

      • reticulocyte count:

        reduced

      • bone marrow aspirate:

        reduced cellularity, haemophagocytosis

      • bone marrow trephine biopsy:

        reduced cellularity, granulomas, fibrosis

      • bone marrow culture:

        positive for organism

      Other investigations
      • sputum culture:

        positive atypical mycobacterial culture

      Uncommon

      Acute myeloid leukaemia

      History

      more common in older adults (but could be any age); rapid onset of fatigue, shortness of breath, fever, rigors

      Exam

      lymphadenopathy, hepatosplenomegaly, mucosal bleeding

      1st investigation
      • peripheral blood film:

        blasts on blood film, presence of Auer's rods

      • serum prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, D-dimer:

        may be abnormal; suspect disseminated intravascular coagulation

      • bone marrow aspiration:

        usually hypercellular with blasts, rarely hypocellular

        More
      • bone marrow biopsy:

        presence of blasts, infiltration, Auer's rods

      • immunophenotyping:

        detection of clonal population of blasts

      • cytogenetics:

        identification or non-random chromosomal abnormalities

      Other investigations

        Acute lymphoblastic leukaemia (ALL)

        History

        rapid onset of fatigue, shortness of breath, fever, rigors

        Exam

        fever, lymphadenopathy, hepatosplenomegaly, gum infiltration, pallor, petechiae, purpura; papilloedema, nuchal rigidity, and meningismus

        1st investigation
        • peripheral blood film:

          blasts may or may not be present

        • bone marrow aspirate:

          hypercellular with blasts; occasionally hypocellular (childhood ALL)

        Other investigations
        • immunophenotyping (of peripheral blood or bone marrow):

          detection of clonal population of blasts; specific lymphoid lineage; clinically important cell surface antigens

        • cytogenetics:

          may detect cytogenetic abnormalities (e.g., Philadelphia chromosome)

        Multiple myeloma

        History

        gradual onset of fatigue, weight loss, fever, rigors, back pain, constipation (due to hypercalcaemia), bone pain

        Exam

        pallor, vertebral collapse; less commonly hyperviscosity syndrome (purpura, visual defects, confusion, neuropathy)

        1st investigation
        • peripheral blood film:

          stacked red blood cells (rouleaux formation), circulating plasma cells may rarely be present

        • bone marrow aspirate:

          plasma cell infiltrate, abnormal plasma cells, plasmablasts

        • immunophenotyping (of peripheral blood or bone marrow):

          plasma cells exhibit restriction of kappa or lambda light chain expression

        • serum and urine immunofixation:

          paraprotein band (IgG, IgA, IgM, IgD, or IgE; and kappa or lambda light chain)

        Other investigations
        • radiological skeletal survey:

          lytic lesions and/or osteopenia

        Myelofibrosis

        History

        gradual onset of fatigue, weight loss, fever, night sweats, left upper quadrant discomfort

        Exam

        cachexia, pallor, splenomegaly, hepatomegaly

        1st investigation
        • peripheral blood film:

          leuko-erythroblastic, teardrop-shaped red blood cells

        • bone marrow aspirate:

          hypercellular and fibrotic, often dry tap and non-diagnostic

        Other investigations
        • serum and red blood cell folate:

          usually diminished

        • serum B12:

          usually elevated

        Lysosomal storage disorders

        History

        gradual onset of fatigue, fever, rigors, bone pain, abdominal discomfort, fractures, spontaneous bruising, or mucosal bleeding

        Exam

        pallor, splenomegaly or hepatosplenomegaly, purpura and petechiae

        1st investigation
        • leukocyte glucocerebrosidase activity:

          reduced or absent

        • peripheral blood film:

          pancytopenia

        • reticulocyte count:

          may be high, normal, or reduced

        • bone marrow aspirate:

          substrate-laden macrophages in Gaucher's disease

        Other investigations
        • bleeding time:

          prolonged

        Anorexia nervosa

        History

        may be a prior history of eating disorder, distorted body image and self-harming behaviour, amenorrhoea

        Exam

        decreased body mass index, parotid swelling, lanugo hair, bradycardia, hypotension

        1st investigation
        • peripheral blood film:

          red cell acanthocytes, poikilocytosis and basophilic stippling

        • reticulocyte count:

          low

        • bone marrow aspirate:

          hypocellular, reduced haematopoietic cells, may show gelatinous transformation

        • bone marrow trephine biopsy:

          hypocellular without infiltration or fibrosis

        • diepoxybutane test:

          normal

        Other investigations

          Graft-versus-host disease (GVHD)

          History

          non-irradiated cellular product transfusion in immunocompromised patients, fatigue, spontaneous bruising and/or mucosal bleeding, fever, diarrhoea

          Exam

          rash (particularly hands and feet), jaundice, pallor, purpura, petechiae

          1st investigation
          • peripheral blood film:

            no specific features

          • reticulocyte count:

            low

          • bone marrow aspirate:

            hypocellular, reduced haematopoietic cells, increased macrophages, erythrophagocytosis

          • bone marrow trephine biopsy:

            hypocellular without infiltration or fibrosis, increased macrophages

          • HLA typing of peripheral blood lymphocytes:

            chimerism

            More
          Other investigations
          • skin, liver, upper gastrointestinal biopsy:

            may be necessary to definitively rule in or rule out the diagnosis of GVHD

          • urine, blood, and stool cultures:

            excludes the possibility of infection

          Heavy metal (arsenic) poisoning

          History

          environmental exposure (wood, glass production, semiconductor industry, smelting, pesticides), headaches, abdominal pain

          Exam

          pallor, jaundice, signs of portal hypertension may be present

          1st investigation
          • peripheral blood film:

            basophilic stippling

          • bone marrow aspirate:

            hypocellular without infiltrate or fibrosis, decreased haematopoietic cells, dyserythropoiesis

          • bone marrow trephine biopsy:

            hypocellular without infiltration or fibrosis dyserythropoiesis

          • diepoxybutane test:

            normal

          • flow cytometry for paroxysmal nocturnal haemoglobinuria clone:

            negative

          • arsenic level (serum, urine, hair, nails):

            elevated

            More
          Other investigations

            Parvovirus infection in sickle cell anaemia (and other haemolytic anaemias)

            History

            weakness, lethargy secondary to associated aplastic crisis

            Exam

            pallor, rash

            1st investigation
            • FBC:

              drop in haemoglobin concentration of >30% secondary to complete arrest of erythropoiesis

            • reticulocyte count:

              decrease or absence of measurable reticulocytes

            • bone marrow biopsy:

              remarkable for severe aplasia

            Other investigations

              Dyskeratosis congenita (DC)

              History

              presents in the third or fourth decade of life, fatigue, spontaneous bruising and mucosal bleeding, fever, rigors (less common), chronic tearing, difficulty with urination

              Exam

              nail and skin atrophy, blocked tear ducts, urethral meatal stenosis, reticulated skin pigmentation, pallor, purpura, petechiae

              1st investigation
              • peripheral blood film:

                red cells usually macrocytic

              • reticulocyte count:

                low or absent

              • bone marrow aspirate:

                hypocellular, reduced haematopoietic cells, dyserythropoiesis common

              • bone marrow trephine biopsy:

                hypocellular without infiltration or fibrosis

              • diepoxybutane test:

                normal (peripheral blood lymphocytes)

              • flow cytometry for paroxysmal nocturnal haemoglobinuria (PNH) clone:

                may be present

                More
              • peripheral blood and/or bone marrow immunophenotyping:

                normal

              • blood and/or bone marrow cytogenetics:

                clonal abnormalities present in some patients

              Other investigations
              • genetic studies:

                may identify one of several genetic mutations

                More
              • telomere length:

                abnormally short; length in lymphocytes and granulocytes <1 percentile for age

              Paroxysmal nocturnal haemoglobinuria (PNH)

              History

              previous venous thrombosis, fatigue, intermittent abdominal pain and dark urine, blood in stool

              Exam

              pallor, jaundice, portal hypertension

              1st investigation
              • peripheral blood film:

                polychromasia

              • reticulocyte count:

                relative reticulocytosis

              • bone marrow aspirate:

                hypocellular, reduced haematopoietic cells, mast cells may be increased

              Other investigations
              • diepoxybutane test:

                normal

              • flow cytometry for PNH clone:

                positive

                More

              Idiopathic aplastic anaemia

              History

              seronegative hepatitis, exposure to drugs; rapid onset of fatigue, fever, rigors, spontaneous bruising, mucosal bleeding

              Exam

              pallor, oedema, purpura, petechiae, stomatitis

              1st investigation
              • peripheral blood film:

                normocytic or mildly macrocytic red blood cells, no immature precursors present

              • serum reticulocyte count:

                low or absent

              • bone marrow aspirate:

                hypocellular, mild dyserythropoiesis common

              • bone marrow trephine biopsy:

                hypocellular without fibrosis or infiltrate

              • diepoxybutane (DEB) test (peripheral blood lymphocytes):

                normal

                More
              • flow cytometry for paroxysmal nocturnal haemoglobinuria (PNH) clone:

                may be detectable in up to 30% of patients

                More
              • peripheral blood, bone marrow immunophenotyping:

                normal

              • peripheral blood, bone marrow cytogenetics:

                abnormal clones present in a minority of patients

              Other investigations
              • genetic testing:

                may identify genetic abnormality

                More

              Fanconi's anaemia

              History

              thrombocytopenia, leukopenia preceding pancytopenia, prior cardiac or genitourinary abnormalities, fatigue, spontaneous bruising and mucosal bleeding, fever, rigors; may have long history of abnormal findings

              Exam

              short stature, structural abnormalities of upper and lower limbs, eyes, ears, gonads; hyperpigmentation, café au lait spots, purpura, petechiae

              1st investigation
              • peripheral blood film:

                red blood cells usually macrocytic

              • reticulocyte count:

                low or absent

              • bone marrow aspirate:

                hypocellular dyserythropoiesis

              • diepoxybutane test (peripheral blood lymphocytes):

                increased chromosomal breakage

              Other investigations
              • genetic testing:

                will identify the mutation in most cases

              Other rare inherited cytopenias (e.g., Diamond Blackfan anaemia, Shwachman Diamond syndrome, amegakaryocytic thrombocytopenia)

              History

              anaemia and/or thrombocytopenia, leukopenia preceding pancytopenia, prior congenital anomalies characteristic of any of these syndromes (e.g., cardiac, skeletal, genitourinary, orofacial); fatigue, spontaneous bruising and mucosal bleeding, fever, rigors; may have a long history of abnormal findings in particular single cell cytopenias

              Exam

              short stature, characteristic structural abnormalities of upper and lower limbs, eyes, and ears; pallor, purpura, petechiae

              1st investigation
              • peripheral blood film:

                red blood cells usually macrocytic

              • reticulocyte count:

                low or absent

              • bone marrow aspirate:

                hypocellular dyserythropoiesis

              • fetal haemoglobin and erythrocyte adenosine deaminase activity (Diamond Blackfan anaemia):

                elevated

              • pancreatic enzymes:

                abnormal (in particular stool elastase; Shwachman Diamond syndrome)

              Other investigations
              • genetic testing:

                may identify genetic abnormality

                More

              Idiopathic portal hypertension

              History

              gastrointestinal bleeding secondary to oesophageal varices, no history of liver disease

              Exam

              pallor, ascites, splenomegaly, hepatomegaly, oedema

              1st investigation
              • peripheral blood film:

                no specific features

              • reticulocyte count:

                elevated or normal

              • serum liver function tests:

                normal or mildly elevated

              Other investigations
              • bone marrow aspirate:

                hypercellular, erythroid hyperplasia

              • bone marrow trephine biopsy:

                hypercellular, erythroid hyperplasia

              Chronic myeloid leukaemia

              History

              fever, chills, malaise, weight loss, anorexia

              Exam

              splenomegaly

              1st investigation
              • peripheral blood film:

                myeloid maturing cells, elevated basophils, eosinophils

              • cytogenetics:

                Philadelphia chromosome positive

              • bone marrow biopsy:

                granulocytic hyperplasia

              Other investigations
              • quantitative reverse transcription polymerase chain reaction:

                identification of size and splice type, and detection and quantitation of BCR::ABL fusion

              Brucellosis

              History

              travel to high risk areas (e.g., the Mediterranean Basin [Portugal, Spain, Southern France, Italy, Greece, Turkey, North Africa], Mexico, South and Central America, Eastern Europe, Asia, Africa, the Caribbean, the Middle East); fever; myalgia

              Exam

              splenomegaly, hepatomegaly, pallor, purpura, petechiae

              1st investigation
              • peripheral blood film:

                no specific features

              • bone marrow aspirate:

                trilineage hypercellularity, haemophagocytosis

              • blood and bone marrow cultures:

                positive for organism

              Other investigations

                Leishmaniasis

                History

                fever, lymphadenopathy, skin discoloration

                Exam

                lymphadenopathy, splenomegaly, hepatomegaly, pallor, purpura, petechiae

                1st investigation
                • peripheral blood film:

                  stacked red blood cells (rouleaux formation); organisms rarely seen in peripheral blood film

                • bone marrow aspirate:

                  trilineage hypercellularity; organisms may be seen within macrophages (Leishman-Donovan bodies)

                • bone marrow trephine biopsy:

                  trilineage hypercellularity, haemophagocytosis, small granulomata

                • polymerase chain reaction on peripheral blood or bone marrow aspirate:

                  positive for organism

                Other investigations
                • microscopic examination of relevant specimen:

                  amastigote form of the Leishmania species in macrophages or monocytes

                Haemophagocytosis syndromes

                History

                may be primary (e.g., haemophagocytic lymphohistiocytosis) or secondary to a systemic disorder (e.g., T-cell lymphoma), malaise, fatigue, erythematous skin rash, abdominal discomfort

                Exam

                fever, lymphadenopathy, hepatosplenomegaly, neurological findings in familial disorder (e.g., irritability, neck stiffness, hypotonia, hypertonia, convulsions, cranial nerve palsies, ataxia, haemiplegia, quadriplegia, blindness, coma)

                1st investigation
                • peripheral blood film:

                  no specific features

                • bone marrow aspirate:

                  trilineage hypercellularity, haemophagocytosis

                • blood and bone marrow cultures:

                  positive for organism

                Other investigations
                • autoimmune screen:

                  positive antinuclear antibodies (ANA) and anti-ds DNA

                  More
                • serum ferritin:

                  22,470 picomol/L (>10,000 microgram/L or 10,000 ng/mL)

                  More
                • molecular genetic testing:

                  specific karyotype present

                  More

                Drug-induced immune pancytopenia

                History

                drug ingestion (e.g., quinine, sulfonamides, methotrexate, and rifampicin), rapid onset of fatigue, easy bruising, spontaneous bleeding

                Exam

                pallor, purpura, petechiae, rarely mild splenomegaly, mild jaundice

                1st investigation
                • platelet-specific antibodies:

                  positive

                • peripheral blood film:

                  no specific features

                • reticulocyte count:

                  elevated

                • bone marrow aspirate:

                  hypercellular

                • bone marrow trephine biopsy:

                  hypercellular

                Other investigations

                  Evans syndrome with associated neutropenia

                  History

                  fatigue, dark urine, jaundice, easy bruising, spontaneous mucosal bleeding

                  Exam

                  pallor, purpura, petechiae; lymphadenopathy and hepatosplenomegaly, which may be subtle with a duration >6 months

                  1st investigation
                  • peripheral blood film:

                    polychromasia, spherocytes

                  • reticulocyte count:

                    elevated

                  • direct antiglobulin test:

                    positive

                  • platelet, neutrophil-specific antibodies:

                    positive

                  • bone marrow aspirate:

                    normal or trilineage hypercellularity

                  • bone marrow trephine biopsy:

                    normal or trilineage hypercellularity

                  Other investigations
                  • further tests for autoimmune lymphoproliferative syndrome (ALPS):

                    may be increased double-negative T cells; defective lymphocyte apoptosis; known ALPS-related germ-line pathological mutation or positive results from other functional assays

                    More

                  Autoimmune lymphoproliferative syndrome (ALPS)

                  History

                  bicytopenia or pancytopenia, other organs (e.g., the liver) may cause symptoms, may be a family history; in children with autoimmune bicytopenia or pancytopenia (Evans syndrome), a diagnostic work-up for ALPS is strongly suggested​

                  Exam

                  splenomegaly and/or lymphadenopathy for >6 months, which may be subtle

                  1st investigation
                  • T-cell analysis:

                    increased double-negative T cells

                  • lymphocyte apoptosis:

                    may be defective

                  • genetic analysis:

                    ALPS-related germ-line mutation may be detected

                  Other investigations

                    Systemic lupus erythematosus

                    History

                    established connective tissue disorder, joint pain, swelling, fatigue, easy bruising

                    Exam

                    synovitis, joint deformity, malar rash, splenomegaly

                    1st investigation
                    • peripheral blood film:

                      stacked red blood cells (rouleaux formation)

                    • autoimmune screen:

                      positive antinuclear antibodies and anti-double stranded DNA

                    • ultrasound of the abdomen:

                      splenomegaly

                    • bone marrow aspirate:

                      hypocellular, dysplastic changes, haemophagocytosis

                    • bone marrow trephine biopsy:

                      hypocellular, benign lymphoid aggregates, bone marrow fibrosis

                    Other investigations

                      Rheumatoid arthritis

                      History

                      established connective tissue disorder, joint pain, swelling, fatigue, easy bruising

                      Exam

                      synovitis, joint deformity

                      1st investigation
                      • peripheral blood film:

                        stacked red blood cells (rouleaux formation)

                      • autoimmune screen:

                        positive rheumatoid factor

                      • bone marrow aspirate:

                        hypocellular, dysplastic changes, haemophagocytosis

                      • bone marrow trephine biopsy:

                        hypocellular, benign lymphoid aggregates

                      • ultrasound of the abdomen:

                        splenomegaly

                      Other investigations

                        Infectious mononucleosis

                        History

                        malaise, headache, low-grade fever

                        Exam

                        tonsillitis, pharyngitis, cervical lymphadenopathy, nodal tenderness

                        1st investigation
                        • serum monospot:

                          positive

                        • peripheral blood film:

                          atypical lymphocytes

                        • Epstein-Barr nuclear antibody:

                          present

                        • blood serology (specific IgM and IgG titres) for viral capsid antigen:

                          positive

                        Other investigations

                          Felty syndrome

                          History

                          rheumatoid arthritis, typically precedes other findings, may be long-standing (>10 years' duration)

                          Exam

                          splenomegaly

                          1st investigation
                          • bone marrow biopsy:

                            myeloid hyperplasia with excess of immature forms

                          • autoimmune screen:

                            positive rheumatoid factor

                          • ultrasound of the abdomen:

                            splenomegaly

                          Other investigations
                          • FBC:

                            neutrophil count <2000/microlitre, anaemia, thrombocytopenia

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