Haematologic conditions such as leukaemia, lymphoma and the anaemias can be difficult to diagnose. The history is an important first step in this diagnosis, and provides information about the patient's baseline level of function prior to presentation.
Start by asking the patient what their main reason for presenting was.
- Common symptoms in haematologic disorders include:
- Constitutional symptoms - fatigue, lethargy, malaise, weight loss, night sweats
- Symptoms of anaemia - Fatigue, shortness of breath, reduced exercise tolerance, lightheadedness, worsening angina, ankle swelling
- Symptoms of neutropaenia - mouth ulcers, skin infections, other recurrent infections
- Symptoms of bleeding diathesis - easy bruising, epistaxis, gum bleeding, joint pain / swelling
- Symptoms of lymphoma - enlarged / painful lymph nodes, painful splenomegaly, B symptoms
- Symptoms of hyperviscosity - neuropathy, epistaxis, blurred vision, headache
- Symptoms of venous thromboembolism - limb pain / swalling, chest pain, shortness of breath, palpitations
Patients with haematologic disorders are often also referred in because they have abnormal blood tests; they may themselves be asymptomatic.
History of Presenting Complaint
When asking for more information about a patient’s symptoms, start by asking general questions such as “could you please tell me more about that”, and then narrow down the questions as more information is provided.
- Generally speaking, the following questions are a good starting point for any type of pain, and may be useful in gaining information about other symptoms:
- Site - localised or generalised; unilateral or bilateral
- Onset - sudden or gradual, and what the situation was (e.g. following trauma)
- Character - sharp, dull, burning or pressure-like
- Radiation - e.g. down the arm or across the back
- Associated symptoms - e.g. fevers, nausea / vomiting, bony pain
- Timing - duration of symptoms, frequency of episodes, changes through the day
- Exacerbating & alleviating factors - e.g. exacerbation with exertion and alleviation with rest
- Severity - on a scale of 1 to 10, with 10 being the worst
Past Medical History
Ask about any medical conditions the patient has previous been diagnosed with, the management of these conditions, and any complications they may have.
- Common haematologic disorders include:
- Haematologic malignancy - AML, ALL, CML, CLL, myeloma, lymphoma
- Myeloproliferative neoplasms - polycythaemia vera, essential thrombocytosis, myelofibrosis
- Myelodysplastic syndrome
- Anaemias - aplastic anaemia, iron deficiency Anaemia, anaemia of chronic disease, haemolytic anaemia, thalassaemias, sickle cell anaemia
- Bleeding disorders - haemophilias, Von Willebrand disease
- Thrombotic disorders - DVT / PE, antiphospholipid syndrome
- Platelet disorders - ITP, DIC, TTP, HUS, HELLP, HITS
Ask about a history of recurrent infections, which suggests immunosuppression and may occur in patients with neutropaenia.
Also ask about excessive bleeding or bruising in the past, which may be a symptom of platelet disorders or coagulopathy.
Ask about whether the patient has recieved any transfusions in the past, and whether they recieved red blood cells, platelets or plasma products.
Ask about any previous transfusion reactions (infectious or non-infectious), and whether the patient has any known antibodies.
Patients with certain haematologic disorders will have had an autologous or allogeneic stem cell transplant in the past.
An autologous stem cell transplant involves mobilising and collecting a patient's stem cells, providing chemotherapy to deplete the bone marrow, and then retransfusing their stem cells. This process is less complex and has less potential side effects than an allogeneic stem cell transplant.
An allogeneic stem cell transplant involves depleting a patient's bone marrow using chemotherapy, and then transfusing another (matched) patient's stem cells. This serves purposes of both replacing their haematopoietic cells with normal cells, and providing some degree of graft-vs-disease effect.
Ask about what medications the patient takes regularly, what they take them for, and what side effects they have had.
- A large number of drugs cause haematologic side effects. These include:
- Bleeding - NSAIDs, antiplatelets, SSRIs
- Thrombosis - oral contraceptives, hormone replacement, COX-2 inhibitors, erythropoietin, warfarin (initially)
- Anaemia - a large number of drugs may cause immune haemolysis, thrombotic microangiopathy, megaloblastic anaemia, sideroblastic anaemia, aplastic anaemia, pure red cell aplasia, or haemolysis in patients with G-6-PD deficiency
- Erythrocytosis - anaobolic steroids, erythropoietin
- Thrombocytopaenia - certain drugs may cause immune thrombocytopaenia, thrombotic microangiopathy or heparin-induced thrombocytopaenia
- Neutropaenia - NSAIDs, antipsychotics, anticonvulsants, antithyroid drugs, antibiotics, chemotherapy
- Neutrophilia - corticosteroids, adrenaline, lithium, G-CSF
- Eosinophilia - any cause of drug allergy; particularly penicillins, cephalosporins, phenytoin, carbamazepine, H2 blockers, PPIs
Ask about a family history of haematologic malignancy, such as AML, ALL, CML, CLL, myeloma or lymphoma.
Also ask about a family history of inherited haematologic disorders such as haemochromatosis, haemophilia, Von Willebrand’s disease or thalassaemia.
It is important to understand any patient’s social situation when taking their history. This includes key aspects such as their occupation (or previous occupation, if retired), living situation, mobility, ability to perform activities of daily living, diet and exercise.
In patients with suspected venous thromboembolism, ask about recent long-haul travel - particularly long flights.
Ask about alcohol intake, as alcohol abuse is associated with bone marrow suppression and myelodysplasia. Ask how many drinks the patient has per week, what type of drinks, and whether they have considered cutting down their intake if heavy.
Al-Nouri ZL, Reese JA, Terrell DR, Vesely SK, George JN. Drug-induced thrombotic microangiopathy: a systematic review of published reports. Blood. 2014 Jan 1:blood-2014.Arndt PA, Garratty G. The changing spectrum of drug-induced immune hemolytic anemia. InSeminars in hematology 2005 Jul 1 (Vol. 42, No. 3, pp. 137-144). WB Saunders.Aster RH, Bougie DW. Drug-induced immune thrombocytopenia. New England Journal of Medicine. 2007 Aug 9;357(6):580-7.Aster RH, Curtis BR, McFarland JG, Bougie DW. Drug?induced immune thrombocytopenia: pathogenesis, diagnosis, and management. Journal of Thrombosis and Haemostasis. 2009 Jun;7(6):911-8.Beutler E. G6PD deficiency. Blood. 1994 Dec 1;84(11):3613-36.Bhatt V, Saleem A. Drug-induced neutropeniapathophysiology, clinical features, and management. Annals of Clinical & Laboratory Science. 2004 Apr 1;34(2):131-7.Bing RJ, Lomnicka M. Why do cyclo-oxygenase-2 inhibitors cause cardiovascular events?.Bubp J, Jen M, Matuszewski K. Caring for glucose-6-phosphate dehydrogenase (G6PD)deficient patients: Implications for pharmacy. Pharmacy and Therapeutics. 2015 Sep;40(9):572.Chan FC, Lau KK, Chan AK, Chan HH. Tranexamic acid is a weak provoking factor for thromboembolic events: A systematic review of the literature.Davis JM, Albert JD, Tracy KJ, Calvano SE, Lowry SF, Shires GT, Yurt RW. Increased neutrophil mobilization and decreased chemotaxis during cortisol and epinephrine infusions. The Journal of trauma. 1991 Jun;31(6):725-31.Dlott JS, Danielson CF, Blue?Hnidy DE, J McCarthy L. Drug?induced thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a concise review. Therapeutic Apheresis and Dialysis. 2004 Apr;8(2):102-11.Frank JE. Diagnosis and management of G6PD deficiency. American family physician. 2005 Oct;72(7):1277-82.Garbe E, Andersohn F, Bronder E, Salama A, Klimpel A, Thomae M, Schrezenmeier H, Hildebrandt M, Späth-Schwalbe E, Grüneisen A, Meyer O. Drug-induced immune thrombocytopaenia: results from the Berlin CaseControl Surveillance Study. European journal of clinical pharmacology. 2012 May 1;68(5):821-32.Hesdorffer CS, Longo DL. Drug-induced megaloblastic anemia. New England Journal of Medicine. 2015 Oct 22;373(17):1649-58.Kaferle J, Strzoda CE. Evaluation of macrocytosis. American family physician. 2009 Feb 1;79(3).Kast RE. How lithium treatment generates neutrophilia by enhancing phosphorylation of GSK-3, increasing HIF-1 levels and how this path is important during engraftment. Bone marrow transplantation. 2008 Jan;41(1):23.
Kaufman DW, Kelly JP, Jurgelon JM, Anderson T, Issaragrisil S, Wiholm BE, Young NS, Leaverton P, Levy M, Shapiro S. Drugs in the aetiology of agranulocytosis and aplastic anaemia. European Journal of Haematology. 1996 Dec;57(S60):23-30.Kim Y, Bang OY. Paradoxical procoagulant effect of early doses of warfarin: possible role of non-vitamin K oral anticoagulant in patients with atrial fibrillation-related stroke. Journal of stroke. 2015 May;17(2):216.Lacy P. Mechanisms of degranulation in neutrophils. Allergy, Asthma & Clinical Immunology. 2006 Sep;2(3):98.Low MS, Vilcassim S, Fedele P, Grigoriadis G. Anabolic androgenic steroids, an easily forgotten cause of polycythaemia and cerebral infarction. Internal medicine journal. 2016 Apr;46(4):497-9.Marsh JC, Ball SE, Cavenagh J, Darbyshire P, Dokal I, Gordon?Smith EC, Keidan J, Laurie A, Martin A, Mercieca J, Killick SB. Guidelines for the diagnosis and management of aplastic anaemia. British journal of haematology. 2009 Oct;147(1):43-70.Means RT. Pure red cell aplasia. Blood. 2016 Jan 1:blood-2016.Mintzer DM, Billet SN, Chmielewski L. Drug-induced hematologic syndromes. Advances in hematology. 2009;2009.Noris M, Remuzzi G. Atypical hemolyticuremic syndrome. New England Journal of Medicine. 2009 Oct 22;361(17):1676-87.
Patel JN, Jiang C, Hertz DL, Mulkey FA, Owzar K, Halabi S, Ratain MJ, Friedman PN, Small EJ, Carducci MA, Mahoney JF. Bevacizumab and the risk of arterial and venous thromboembolism in patients with metastatic, castration?resistant prostate cancer treated on Cancer and Leukemia Group B (CALGB) 90401 (Alliance). Cancer. 2015 Apr 1;121(7):1025-31.
Pintova S, Bhardwaj AS, Aledort LM. IVIGa hemolytic culprit. New England Journal of Medicine. 2012 Sep 6;367(10):974-6.Ramot Y, Nyska A, Spectre G. Drug-induced thrombosis: an update. Drug safety. 2013 Aug 1;36(8):585-603.Rauscher C, Freeman A. Drug-induced eosinophilia. InAllergy & Asthma Proceedings 2018 May 1 (Vol. 39, No. 3).Reese JA, Li X, Hauben M, Aster RH, Bougie DW, Curtis BR, George JN, Vesely SK. Identifying drugs that cause acute thrombocytopenia: an analysis using three distinct methods. Blood. 2010 Jan 1:blood-2010.Salama A. Drug-induced immune hemolytic anemia. Expert opinion on drug safety. 2009 Jan 1;8(1):73-9.Saste VV, Terrell DR, Vesely SK, George JN. Drug-Associated Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS): Frequency, Presenting Features, and Clinical Outcomes.Serebruany VL. Selective serotonin reuptake inhibitors and increased bleeding risk: are we missing something?. The American journal of medicine. 2006 Feb 1;119(2):113-6.Soloway HB. Drug-induced bleeding. American journal of clinical pathology. 1974 May 1;61(5):622-7.Stroncek DF. Drug-induced immune neutropenia. Transfusion medicine reviews. 1993 Oct;7(4):268-74.Sundström A, Seaman H, Kieler H, Alfredsson L. The risk of venous thromboembolism associated with the use of tranexamic acid and other drugs used to treat menorrhagia: a casecontrol study using the General Practice Research Database. BJOG: An International Journal of Obstetrics & Gynaecology. 2009 Jan 1;116(1):91-7.Tenner S, Rollhauser C, Butt F, Gonzalez P. Sideroblastic anemia: A diagnosis to consider in alcoholic patients. Postgraduate medicine. 1992 Nov 15;92(7):147-50.Tesfa D, Keisu M, Palmblad J. Idiosyncratic drug?induced agranulocytosis: possible mechanisms and management. American journal of hematology. 2009 Jul;84(7):428-34.Tobu M, Iqbal O, Fareed D, Chatha M, Hoppensteadt D, Bansal V, Fareed J. Erythropoietin-induced thrombosis as a result of increased inflammation and thrombin activatable fibrinolytic inhibitor. Clinical and applied thrombosis/hemostasis. 2004 Jul;10(3):225-32.Visentin GP, Liu CY. Drug-induced thrombocytopenia. Hematology/oncology clinics of North America. 2007 Aug 1;21(4):685-96.
Wickramasinghe SN. Diagnosis of megaloblastic anaemias. Blood reviews. 2006 Nov 1;20(6):299-318.
Williams C. Drug-induced eosinophilia. Lung cancer. 2018 Jun 12;15:05.Yang Y, Li Z, Nan P, Zhang X. Drug-induced glucose-6-phosphate dehydrogenase deficiency-related hemolysis risk assessment. Computational biology and chemistry. 2011 Jun 1;35(3):189-92.