Haematology Flashcards
Myeloma
Malignancy of plasma cells leads to large quantities of a single type of antibody being produced. Most commonly IgG, sometimes IgA.
Terminal with relapsing-remitting course.
C: Increased risk if male, older, Afro-Caribbean ethnicity, obese, family history.
S: Hypercalcaemia, renal failure, anemia, neutropenia and thrombocytopenia, bone lesions/pain, easy bruising/bleeding.
D: FBC, Calcium, ESR, bone marrow biopsy, serum and/or urine electrophoresis, X-ray, CT/MRI.
T: Chemotherapy (lenalidomide, bortezomib, dexamethasone), Autologous stem cell transplant, analgesia, Bisphosphonates to prevent further lesions, iron infusion, rehydration and dialysis used for renal failure, treat infections as they occur.
Acute Myeloid Leukaemia
A malignant disease of the bone marrow in which precursors of blood cells are arrested in an early stage of development.
C: Activation of abnormal genes through chromosomal translocations and other genetic abnormalities.
S: Fatigue, dizziness and shortness of breath, fevers not affected by antibiotics, bleeding, splenomegaly, bone pain, thrombocytopenia (petechiae), gingivitis.
D: FBC (anaemia and thrombocytopenia), clotting (DIC), raised lactate dehydrogenase, raised uric acid, Bone marrow aspiration, CXR, ECG, Multiple-gated acquisition (MUGA) scan.
T: Induction (to attain remission). The standard combination for induction is cytarabine and daunorubicin. Post-remission consolidation (intensification).
Stem cell transplantation for intermediate- and high-risk AML
Other aspects of care include blood product replacement, antibiotics for infection and allopurinol to reduce uric acid levels.
Acute Lymphoblastic Leukaemia
A malignant transformation of a clone of cells from lymphoid progenitor cells, usually B cells. They replace the normal cells of the bone marrow.
C: Genetic, environment, infection.
Risk factors - trisomy 21, radiation, insulation from common infections early in life.
S: Fatigue, dizziness, palpitations, bone pain, recurrent infections, fever not due to infection, dyspnoea, headache, irritability, menorrhagia, frequent nosebleeds, spontaneous bruising, petechiae, abdominal distension, lymphadenopathy, testicular enlargement.
D: FBC, blood film, clotting (DIC), lactate dehydrogenase, uric acid, CXR, ECG, bone marrow aspiration and biopsy.
T: Replacement therapy of blood cells, treat infection, allopurinol, Pre-phase therapy with corticosteroids (usually prednisone or dexamethasone).
Most induction regimens are centred on vincristine, corticosteroids, and anthracycline, with or without cyclophosphamide or cytarabine.
Once normal haematopoiesis is achieved, patients undergo maintenance therapy - daily 6-mercaptopurine and weekly methotrexate.
Chronic Myeloid Leukaemia
A myeloproliferative disorder of pluripotent haemopoietic stem cells, affecting one or all cell lines (erythroid, platelet and myeloid).
C: Unknown. But characterised by a consistent cytogenetic abnormality in the Philadelphia chromosome.
S: Fatigue, night sweats, weight loss, abdominal distension, splenomegaly, hepatomegaly, enlarged lymph nodes, anaemia, easy bruising, fever, gout.
D: FBC, peripheral blood smear, lactate dehydrogenase, uric acid, bone marrow aspiration and biopsy, cytogenetics,
T: Tyrosine kinase inhibitors (TKIs) - Imatinib. When drug resistance occurs, second-generation drugs such as nilotinib and dasatinib. Bone marrow transplant in the chronic phase (up to 24 months since diagnosis).
Chronic Lymphoblastic Leukaemia
A malignant monoclonal expansion of B lymphocytes with accumulation of abnormal lymphocytes in the blood, bone marrow, spleen, lymph nodes and liver.
C: Unknown. May have a genetic basis.
S: Recurrent infection, enlarged lymph nodes, abdominal discomfort, bleeding or petechiae in skin or mucous membranes - from thrombocytopenia, fatigue, splenomegaly, hepatomegaly.
D: FBC, Peripheral blood smear, Direct antiglobulin test, Bone marrow aspirate, lymph node biopsy, Immunophenotyping.
T: No cure. Watch and wait, bloods every 3-12 months. Chemotherapy should only be given to patients with active, symptomatic disease - continuous or intermittent treatment with chlorambucil or cyclophosphamide. Bendamustine if chemo not suitable. Chemo-immunotherapy with fludarabine, cyclophosphamide and rituximab for relapsed.
Lymphoma
Group of cancers that affect the lymphocytes within the lymphatic system. Malignant cells proliferate within lymph nodes and cause lymphadenopathy.
Can be Hodgkin’s lymphoma or non-Hodgkin’s lymphoma.
C: Unknown. Risk factors - HIV, EBV, family history, also associated with RA and sarcoidosis.
S: Painless swelling of lymph nodes in your neck, armpits or groin, night sweats, weight loss, dyspnoea, itchy skin, fatigue, fever.
D: Lymph node biopsy, lactate dehydrogenase, FBC, ESR, LFT, urate, Ca2+, Imaging (CT, MRI, PET).
T: Chemotherapy ‘ABVD’ system used for HL - doxorubicin (Adriamycin®), bleomycin, vinblastine, dacarbazine.
Radiotherapy
Stem cell transplantation
Watchful waiting may be considered if low-grade.
Anaemia
A low haemoglobin concentration and may be due either to a low red cell mass or increased plasma volume. Can be microcytic (low MCV), normcytic, macrocytic (high MCV).
C: Microcytic - iron-deficiency, thalassemia.
Normocytic - blood loss, bone marrow failure, renal failure, hypothyroidism, haemolysis, pregnancy.
Macrocytic - B12/folate deficiency, excess alcohol, cytotoxics, marrow infiltration, hypothyroidism.
S: Fatigue, dyspnoea, fainting, palpitations, headache, tinnitus, anorexia, conjunctival pallor.
D: FBC, ferritin levels, blood film, TFTs, LFTs, B12/folate
T: If iron-deficiency, oral iron (ferrous sulphate), IV iron. If chronic disease, treat underlying disease. If sideroblastic anaemia, Pyridoxine with/without blood transfusions. If macrocytic, assess for an underlying cause. Treat with folate and B12. If pernicious, B12 oral or IM.
Transfuse if Hb<70g/L.
B12 deficiency
Low levels of vitamin B12 in the body. B12 is used to synthesise DNA precursors, which are important for cell division.
C: Impaired absorption: pernicious anaemia which leads to increased IgA antibodies against intrinsic factor, Crohn’s disease whereby the enterocytes are damaged, gastric bypass where food passes too quickly, fish tapeworm, bacterial overgrowth, decreased dietary intake.
S: Anaemia - pallor, shortness of breath, easy fatiguability, soreness of the tongue due to glossitis
Ischemic heart disease - chest pain, slurred speech, paralysis
Impairment of neurological function: loss of memory, decreased reflexes, psychosis
D: FBC (macrocytosis), Homocysteine and methylmalonic acid are elevated, look for anti-intrinsic factor antibodies for pernicious anaemia, endoscopic or imaging studies (for Crohn’s disease).
T: Dietary - supplements
Absorption - high doses of supplements or intramuscular B12 injections
Treatment of the underlying cause
Sickle cell anaemia
B-globin chains end up misshapen due to a mutation in the B-globin gene. Crescent shaped RBC.
C: Autosomal recessive gene - non-conservative missense mutation. Can be a carrier.
S: Intravascular haemolysis leading to anaemia, increased bone production - enlarged cheeks and ‘hair on end’ on an x-ray, hepatomegaly, dactylitis, avascular necrosis, can lead to a stroke, acute chest syndrome, priapism.
D: Newborn blood spot screen, blood smear, protein electrophoresis.
T: Hypoxia, acidosis and dehydration can be improved with oxygen and fluids. Opioids for analgesia. Blood transfusion. Hydroxyurea - increases the amount of gamma globin, increasing the levels of foetal haemoglobin which prevents sickling. Bone marrow transplantation. Gene therapy.
Thalassaemia
Recessively autosomal inherited conditions characterised by decreased or absence of synthesis of one of the two polypeptide chains (α or β) that form the normal adult human haemoglobin.
C: β-globin gene defects may give rise to β thalassaemia, while mutations of the α globin gene may cause α thalassaemia.
S: α - homozygous is lethal, carrier -mild anaemia and low red blood cell,
β - failure to thrive, vomiting feeds, sleepiness, stunted growth and irritability.
Severe - hepatomegaly, bony deformities, pallor, jaundice, exercise intolerance, growth restriction, iron overload.
D: FBC (microcytic, hypochromic anaemia), iron studies, haemoglobin electrophoresis, PCR, skull X-ray, CXR, CT/MRI.
T: Asymptomatic carriers - no treatment. Thalassaemia major - Regular hypertransfusion to maintain a haemoglobin level higher than 9.5 g/dL, iron chelation to prevent overload syndrome (deferasirox and deferiprone)
Education and psychological support
Genetic counselling
Polycythaemia vera
A rare blood cancer that affects the bone marrow. It is sometimes called erythrocytosis which means too many red blood cells.
C: Usually a mutation in a haemopoietic stem cell like JAK2.
S: Fatigue, dizziness, increased sweating, redness in the face, blurred vision, itchy skin, hepatomegaly, gout, kidney stones.
D: Blood test: Increased haemoglobin, haematocrit, white blood cells, platelet count, biopsy to look for signs of fibrosis, Genetic testing for the JAK2 gene mutation.
T: Phlebotomy for autologous donation, Myelosuppressive medication - hydroxyurea or ruxolitinib (Jak2 inhibitor), antihistamines, hydroxyzine, blood transfusions.
Heparin-induced thrombocytopenia
Acquired platelet disorder due to exposed to low-molecular weight heparin.
C: IgG autoantibodies form against LMWH, leading to increased clotting and consumption of platelets.
S: Skin necrosis at injection site, fever, chills, dyspnoea, hypertension, limb ischaemia, organ infarction.
D: HIT immunoassay, functional assay, heparin-induced platelet aggregation.
T: Stopping heparin and starting a non-heparin anticoagulant (fondaparinux, argatroban)
Thromboembolectomy
Idiopathic thrombocytic purpura
Acquired thrombocytopenia
C: Unknown, can be caused viral infections (HIV, hepatitis C, cytomegalovirus), lupus, drug-induced.
S: Bruising easily after minor trauma
Mucocutaneous bleeding (e.g. epistaxis, gingival bleeding, petechiae, purpura).
D: Low platelet count, peripheral blood smear analysis - scarce platelets, flow-cytometry based assays.
T: Glucocorticoids (dexamethasone, prednisone)
Rituximab (monoclonal antibody)
Thrombopoietin (TPO) receptor agonists
Immunosuppressive agents - Danazol, azathioprine, cyclosporine
Thrombotic thrombocytopenia pura
Excessive von Willebrand factor on endothelial surfaces, causing adherence of platelets.
C: Inherited mutation of ADAMTS13 or an acquired inhibitory autoantibody.
S: Renal dysfunction, neurological impairment (headache, confusion, seizures, coma), fever, mucocutaneous bleeding (e.g. epistaxis, gingival bleeding, petechiae, purpura), dark urine, light-headedness, abdominal pain, easy bruising, nausea/vomiting.
D: Blood tests: decreased platelets, increased reticulocyte, decreased haemoglobin
Peripheral blood smear analysis
Elevated lactate dehydrogenase, indirect bilirubin, creatinine
ADAMTS13 assay
T: Glucocorticoids
Monoclonal antibodies
Plasma exchange
Disseminated Intravascular Coagulopathy
A syndrome characterised by the systemic activation of blood coagulation, which generates intravascular fibrin, leading to thrombosis of small- and medium‐sized vessels, and eventually organ dysfunction.
C: Risk factors - infections, malignancy, major trauma, complications of pregnancy, incompatible blood transfusion, transplant rejection, pancreatitis, heat stroke, dissecting aortic aneurysm, recreational drugs, antiphospholipid syndrome.
S: Bleeding from at least three unrelated sites, confusion, fever, signs of haemorrhage, signs of adult respiratory distress syndrome, petechiae, skin necrosis, localised infarction, gangrene.
D: FBC (low platelets), Fibrin degradation products (FDP) including D-dimer are elevated, Prothrombin time (elevated), Activated partial thromboplastin time (aPTT) elevated, fibrinogen level low.
T: Treat underlying cause. Severe hypofibrinogenaemia (<1 g/L) that persists despite FFP replacement, or specific fibrinogen deficiencies may be treated with fibrinogen concentrate or cryoprecipitate.
