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Heather Baid

, Fiona Creed

, and Jessica Hargreaves

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date: 05 May 2021

Erythrocyte disorders


This is defined as a red cell count of > 6 × 1012/L or Hb > 180 g/L.

Primary polycythaemia

Blood cell mass (red cells, white cells, and platelets) increases due to excessive bone marrow production. The resultant increase in blood viscosity can cause cardiovascular, neurological, and vascular complications.


  • Venesection and concurrent volume replacement with crystalloid.

  • Aspirin to decrease platelet function and adhesion.

  • Cytarabine to reduce platelet production.

  • Chemotherapy to depress bone marrow production.

Secondary polycythaemia

Red cell count increases in response to chronic hypoxaemia (e.g. COPD, congenital cyanotic heart disease, adaptation to high altitude).

Sickle-cell anaemia

Sickle-cell haemoglobin (HbS) contains two abnormal beta chains and is inherited as an autosomal-dominant gene. When exposed to low oxygen tensions the red cells become deformed, rigid, and sickle-shaped. The cells aggregate, resulting in the formation of microthrombi in peripheries, causing ischaemia and infarction. Abnormal cells are prematurely destroyed, resulting in a chronic haemolytic anaemia.

Patients with sickle-cell trait (< 50% HbS) are usually symptom-free unless the oxygen tension is very low.

Sickle-cell crisis

Acute haemolytic crises can occur from 6 months of age, and may be precipitated by dehydration and hypoxia. They result in:

  • anaemia

  • jaundice

  • tachycardia

  • cardiomegaly

  • splenic sequestration—causes the spleen to enlarge, impairs splenic function, and increases the risk of overwhelming infection

  • pulmonary sequestration—causes hypoxaemia

  • vaso-occlusion—causes tissue infarction (e.g. in bone, spleen, gut, brain, or lung), leading to severe pain.


  • Correction or prevention of hypoxaemia:

    • Monitor blood gases, oxygen saturation, and Hb. Aim for steady-state values of Hb and oxygen saturation (i.e. when the patient is clinically well). In the steady state Hb may be only 50–90 g/L and SpO2 may be ≥ 90%.

    • Give oxygen therapy, respiratory support, or mechanical ventilation as appropriate.

  • Rehydration:

    • Give fluid replacement (this dilutes the blood and decreases agglutination of sickled cells in small vessels).

    • Avoid fluid overload, as this may precipitate heart failure in patients with cardiomyopathy (a common problem in adult sickle-cell patients).

  • Analgesia:

    • Oral simple analgesics.

    • Opiate or opioid PCA.

  • Infection:

    • Monitor temperature, white cell count, and markers such as CRP.

    • Treat any underlying infection.

    • Patients with splenic dysfunction are prone to infection with encapsulated organisms (e.g. Pneumococcus, Meningococcus), and may require long-term prophylactic penicillin.

  • Blood transfusion:

    • Give an exchange transfusion (e.g. 4 units can be used to reduce HbS levels during severe crises or before elective surgery).

Further reading

Gladwin M and Sachdev V. Cardiovascular abnormalities in sickle cell disease. Journal of the American College of Cardiology 2012; 59: 1123–33.Find this resource:

Howard J. The role of blood transfusion in sickle cell disease. International Society of Blood Transfusion Science Series 2013; 8: 225–8.Find this resource:

Miller AC and Gladwin MT. Pulmonary complications of sickle cell disease. American Journal of Respiratory and Critical Care Medicine 2012; 185: 1154–65.Find this resource:

Leucocyte disorders


This is defined as a neutrophil count of < 2 × 109/L. The risk of developing life-threatening infection is higher with counts of < 1 × 109/L, and such patients are often isolated until the bone marrow recovers. Patients are often asymptomatic until infection develops. Common initial infections include pneumococci, staphylococci, and coliforms. After prolonged immunosuppression and repeated courses of antibiotics, infection with Pseudomonas, fungi (Candida, Aspergillus), TB, cytomegalovirus, or Pneumocystis may occur.


  • Bone marrow failure (leukaemia, myeloma, lymphoma, chemotherapy, radiation).

  • Systemic inflammation following severe infection or trauma (causes aggregation of neutrophils in vital organs).

  • Infections (typhoid, brucellosis, viral, protozoal).

  • Drug related (e.g. carbimazole, sulfonamides).

  • Destruction by neutrophil antibodies (e.g. SLE, rheumatoid arthritis).

  • Deficiency of vitamin B12 or folate (malnutrition).

  • Hypersplenism (increased neutrophil destruction).


  • Compliance with infection prevention and control, and use of aseptic non-touch technique.

  • Discontinuation of implicated drug therapy.

  • Protective isolation if neutrophil count is < 1.0 × 109/L.

  • Avoid uncooked food (e.g. salads).

  • Minimize invasive procedures and monitoring.

  • Personal hygiene, especially skin, eye, and mouth care. Nystatin mouthwashes for oral thrush, and clotrimazole for fungal skin infections.

  • Parenteral antibiotics (broad spectrum if no organism is isolated).

  • Regular surveillance for infection, and specific treatment if infection is identified.

  • Growth factors, such as granulocyte-colony-stimulating factor (G-CSF), to stimulate the bone marrow.


This is a neoplastic disorder of the blood-cell-forming tissues (bone marrow, spleen, and lymphatic system), which causes unregulated and prolific accumulation of white cells in the bone marrow, liver, spleen, and lymph nodes, and invasion of the gastrointestinal tract, meninges, skin, and/or kidneys.


Leukaemia is classified according to the site involved as either acute or chronic. Therapy aims to induce remission by the use of cytotoxic drugs, irradiation, and transplant.

Acute lymphatic leukaemia (ALL)

This is common in children. It is a severe disease in which the lymph nodes, bone, and nervous tissue become infiltrated. Around 50% of children aged 2–11 years survive for 5 years.

Chronic lymphatic leukaemia (CLL)

This occurs mainly in adults aged > 50 years. Patients are often symptom-free. Pleural or peritoneal effusions may develop. No treatment is needed if the patient is asymptomatic. Around 50% survive for 5 years.

Acute myeloid leukaemia (AML)

Any age group may be affected, but AML is more common in adults. Around 30–50% of cases survive long term.

Chronic myeloid leukaemia (CML)

This most commonly occurs in the 30–50 years age group. It has an insidious onset with fever and weight loss. Splenomegaly, hepatomegaly, and thrombocytopenia develop later, with a high white cell count. Survival with chemotherapy is about 3 years. With allogenic bone marrow transplantation, around 50% of patients may survive for more than 5 years.

Further reading

Azoulay É and Darmon M. Acute respiratory distress syndrome during neutropenia recovery. Critical Care 2010; 14: 114.Find this resource:

Dowling M, Meenaghan T and Kelly M. Treating chronic myeloid leukaemia: NICE guidance. British Journal of Nursing 2012; 21: S16–17.Find this resource:

Lee Y and Lockwood C. Prognostic factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia: a systematic review and meta-analysis. International Journal of Nursing Practice 2013; 19: 557–76.Find this resource:

Thrombocyte disorders


This is defined as a platelet count of < 150 × 109/L. Bleeding is unlikely to occur unless the count falls to < 50 × 109/L, unless generalized infection is present. Thrombocytopenia is caused by increased destruction, increased consumption, and/or decreased production of platelets.

Causes of increased destruction or consumption of platelets

  • Idiopathic thrombocytopenic purpura (ITP).

  • Thrombotic thrombocytopenic purpura (TTP).

  • Disseminated intravascular coagulation (DIC).

  • Heparin-induced thrombocytopenia (HIT) syndrome.

  • Sepsis.

  • Haemorrhage.

  • Autoimmune disorders (e.g. AIDS, malaria).

  • Extracorporeal circulation (e.g. dialysis).

  • Hypersplenism.

Causes of decreased platelet production

  • Drugs (e.g. chemotherapy).

  • Uraemia.

  • Megaloblastic anaemia.

  • Marrow infiltration (e.g. leukaemia, carcinoma, lymphoma).

Idiopathic thrombocytopenic purpura (ITP)

This is an autoimmune disorder in which autoantibodies are directed against platelets, considerably shortening their lifespan. It is more common in young adults, particularly following respiratory or gastrointestinal viral infections, and may be acute or chronic.

Clinical manifestations include:

  • petechiae, multiple bruising, and epistaxis

  • prolonged bleeding time but normal coagulation times.


There is no definitive treatment.

  • In the acute form of ITP, steroids tend not to increase the platelet count, but may reduce the incidence of bleeding.

  • Platelet and red cell transfusions are generally avoided unless severe bleeding occurs.

  • In the chronic form of ITP, steroids may cause a rise in platelet count.

  • Intravenous immunoglobulin.

  • Rituximab (an anti-CD20 monoclonal antibody that depletes B cells).

  • Splenectomy, if the patient is unresponsive to medical management.

Thrombotic thrombcytopenic purpura (TTP)

This disorder is characterized by fever, thrombotic microangiopathy (TMA), haemolytic anaemia, neurological symptoms (including drowsiness, transient or permanent strokes, and blindness), and renal dysfunction. TTP has many clinical similarities to haemolytic uraemic syndrome (HUS). However, HUS predominantly affects the kidneys and usually follows a diarrhoeal illness, whereas TTP more frequently affects the brain in adults.


  • Abdominal pain.

  • Purpura (the appearance of red or purple discolouration on the skin that does not blanch when pressure is applied).

  • Fever.

  • Hypertension.

  • Neurological signs.

  • Haematuria (may progress to acute kidney injury).


  • Plasma exchange (using FFP).

  • Steroids.

  • Intravenous immunoglobulin.

  • Rituximab (anti-CD20 monoclonal antibody that depletes B cells).

  • Avoidance of platelet transfusion unless there is severe bleeding.

Drug-induced thrombocytopenia


Numerous drugs can cause thrombocytopenia, including:

  • heparin

  • quinine

  • antituberculous drugs

  • thiazide diuretics

  • penicillins

  • sulfonamides

  • anticonvulsants

  • chemotherapy.

Heparin-induced thrombocytopenia (HIT) syndrome

Antibodies generated during exposure to heparin affect platelet activation and cause endothelial dysfunction. This occurs with all heparins, including low-molecular-weight heparin (LMWH), which forms antibodies against platelets. Most patients who are affected do not suffer clinical consequences. HIT syndrome rarely occurs with transient exposure to heparinoids, typically appearing after 7–10 days of use.


Treatment of drug-induced thrombocytopenia is supportive, and includes discontinuation of heparin. Platelet transfusions may be needed for active bleeding or if platelet levels are very low. For HIT syndrome there should be total avoidance of heparin administration (including the small amounts used in arterial flush solutions). As up to 50% of patients will develop a thromboembolic event if taken off heparin and not continued on another anticoagulant, alternative anticoagulation therapy should be commenced promptly.

Further reading

Barbani F et al. Heparin-induced thrombocytopenia incidence in the ICU: preliminary results. Critical Care 2010; 14 (Suppl. 1 ): P637.Find this resource:

Davies J, Patel P and Zoumot Z. Diagnosing heparin induced thrombocytopenia in critically ill patients. Intensive Care Medicine 2010; 36: 1447–8.Find this resource:

Hunt BJ. Bleeding and coagulopathies in critical care. New England Journal of Medicine 2014; 370: 847–59.Find this resource:

Urden L, Stacy K and Lough M. Critical Care Nursing: diagnosis and management, 7th edn. Mosby: St Louis, MO, 2014.Find this resource:

Watson H, Davidson S and Keeling D. Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition. British Journal of Haematology 2012; 159: 528–40.Find this resource:

Anticoagulation therapy

This is used either to prevent thrombus formation or to prevent extension of an existing thrombus. Haemorrhage is a potential complication. Therefore patients must be observed closely for signs of bleeding:

  • Observe and test urine daily for haematuria.

  • Observe and test tracheal and nasogastric aspirate for blood.

  • Observe cannulae sites, wounds, and drains for bleeding.

  • Observe the skin for purpura and bruising.

  • Perform regular laboratory coagulation screens.

  • Avoid vigorous endotracheal or nasogastric tube suction.

  • Place lines and tubes either after cessation of anticoagulant therapy or after correction of coagulopathy.



Unfractionated heparin inhibits FXa and thrombin, and has a half-life of 45–90 min. LMWH (fractionated heparin) derived from unfractionated heparin inhibits FXa and thrombin, is more predictable, and no monitoring is required (an antiXa test can be used). Its half-life is 4 h. Reversal is with protamine sulfate 1 mg per 80–100 units up to a maximum of 50 mg. Consider rFVIIa if there is active bleeding.

Given intravenously, heparin has a rapid onset of action, with a half-life of 90 min. Overdose can be reversed with protamine sulfate (1 mg neutralizes 100 IU of heparin). Unfractionated heparin given by continuous infusion is recommended for patients with renal failure and for anticoagulation of extracorporeal circuits (e.g. haemofiltration, cardiopulmonary bypass). The dosage is monitored by the activated partial thromboplastin time (APTT).

Low-molecular-weight heparin (e.g. enoxaparin, dalteparin) is now the treatment of choice for:

  • thromboprophylaxis

  • VTE and pulmonary embolus

  • acute coronary syndromes.

Fixed dosages are given and no laboratory monitoring is necessary.


Warfarin inhibits vitamin K to stop production of factors II, VII, IX, and X and anticoagulant proteins C and S.

Given orally, it takes at least 3–5 days of loading to achieve full anticoagulation. Therefore heparin cover should be provided for 72 h when warfarin is commenced. Interactions which may lead to under- or over-anticoagulation (e.g. levels of free warfarin) rise with some drugs (e.g. aspirin, amiodarone). Dosage is controlled using the international normalized ratio (INR), and a ratio of 2:3 is usually targeted for adequate anticoagulation. Excess levels are treated by reducing or temporarily discontinuing warfarin.


  • For non-major bleeding give vitamin K (1–3 mg IV).

  • For major bleeding give vitamin K (5 mg IV) and prothrombin complex concentrate (PCC), 25–50 U/kg.

  • If INR is > 5 but there is no bleeding, withhold or reduce the warfarin dose and investigate the causes of elevated INR.

  • If INR is > 8 but there is no bleeding, give vitamin K (5 mg orally).

  • For surgery that can be delayed for 6–12 h, correct with IV vitamin K.

  • For surgery that cannot be delayed, correct with PCC and IV vitamin K. PCC should not be used to enable elective or non-urgent surgery.

Fresh frozen plasma should not be used for warfarin reversal except with haematology approval.


  • Long-term thromboprophylaxis (e.g. metal heart valves, atrial fibrillation) (see NICE guidance1).

  • Long-term anticoagulation for thrombosis or emboli.

Factor Xa inhibitors (FXaIs) (e.g. rivaroxaban, apixaban)

FXaIs bind with the section of factor Xa that catalyses the activation of factor II (prothrombin), so that no thrombin is present. Direct FXaIs can inhibit free factor Xa, clot-bound factor Xa, and factor Xa bound to the prothrombinase complex. They are indicated for the prevention of thromboembolism in patients with atrial fibrillation, and for the prevention of VTE and pulmonary embolism in patients undergoing major orthopaedic surgery.

There is no specific reversal agent, but the short half-life means that discontinuation of the drug is sufficient to correct most bleeding problems caused by its use. The most effective monitor of the anticoagulant effect is an anti-factor Xa assay. However, no routine laboratory test monitoring of coagulation should be required except possibly in special circumstances, such as renal failure, obesity, or severely underweight patients.


Fondaparinux is a synthetic pentasaccharide with indirect anti-Xa activity. Its half-life is 17 h, and there is no specific reversal agent. Consider recombinant factor VIIa if there is active bleeding.


Clopidogrel is metabolized by CYP450 enzymes to produce the active metabolite that inhibits platelet aggregation. This action is irreversible, so platelets that are exposed to the active metabolite of clopidogrel will be affected for the rest of their lifespan (about 7–10 days). Routine blood monitoring is not required. The platelet count will be unaffected. However, the function of the platelets will be impaired.


  • Single antiplatelet therapy for the prevention of atherothrombotic events in patients with myocardial infarction, ischaemic stroke, or established peripheral arterial disease.

  • Or in combination with aspirin in patients suffering from acute coronary syndrome (ACS) or patients undergoing a stent placement following percutaneous coronary intervention (PCI).

Prostacyclin/epoprostenol (PGI2) or prostin (PGE1)

These drugs inhibit platelet aggregation. The effect stops within 30 min of discontinuation. The main side effect is vasodilation, which can cause flushing, hypotension, and tachycardia.


  • As an alternative to heparin in renal replacement therapy.

  • Pulmonary hypertension.

  • Poor gas exchange in ARDS (nebulized).

  • Digital ischaemia (e.g. severe sepsis, autoimmune disease).

Thrombolytic agents (e.g. streptokinase, tissue plasminogen activator (tPA))

These drugs are used to break down a thrombus that has already formed. Allergic reactions can occur, and are more likely with streptokinase. tPA and newer related agents (e.g. reteplase, tenecteplase) are easier to administer, but need to be given with heparin. Bleeding may be a major complication, and should be corrected with the antifibrinolytic agent tranexamic acid, plus FFP, cryoprecipitate, and red cell transfusion as necessary.


  • Acute myocardial infarction.

  • Stroke.

  • Pulmonary embolism.

  • Distal emboli (e.g. in the leg).

Direct thrombin inhibitors (e.g. lepirudin, argatroban, dabigatran)

Lepirudin is a recombinant form of hirudin (extracted from leeches), whereas argatroban is derived from arginine. Both form an irreversible complex with thrombin. These drugs are unrelated to and not affected by heparin. Antibody formation occurs in approximately 40% of patients treated with lepirudin for > 6 days. These drugs have long half-lives and there are no antidotes, so they are contraindicated in patients with active haemorrhage. Bivalirudin is related to hirudin but is reversible, with a short half-life of only 25 min.


This is a heparinoid given intravenously that has therapeutic similarities to heparin. Its use is generally restricted to treatment of HIT syndrome and VTE prophylaxis, although there is a 10–20% risk of cross-reactivity. No antidote is available.


1 National Institute for Health and Care Excellence (NICE). Atrial Fibrillation: the management of atrial fibrillation. CG180. NICE: London, 2014. this resource:

Further reading

Makris M et al. Guideline on the management of bleeding in patients on antithrombotic agents. British Journal of Haematology 2012; 160: 35–46.Find this resource:

Soff G. A new generation of oral direct anticoagulants. Arteriosclerosis, Thrombosis, and Vascular Biology 2012; 32: 569–74.Find this resource:

Clotting disorders

Disseminated intravascular coagulation (DIC)

DIC is an excessive systematic activation of the coagulation cascade, which causes the generation of thrombin and fibrin within circulating blood, resulting in the formation of microthrombi. The resulting depletion of clotting factors can lead to haemorrhage that may be relatively mild (e.g. into skin, haematuria, or around catheter and drain sites) or severe (e.g. major gastrointestinal bleed). It often arises as a secondary complication of an underlying condition.

Disorders that may trigger DIC

  • Infection (bacterial, viral, or parasitic).

  • Obstetric disorders (e.g. septic abortion, eclampsia, amniotic fluid embolism, placental abruption).

  • Liver disorders (e.g. cirrhosis, cholestasis, acute hepatic necrosis).

  • Malignant disease (e.g. carcinoma, leukaemia).

  • Trauma (e.g. crush injuries, burns).

  • Hypovolaemic shock.

  • Pulmonary embolism or fat embolism.

  • Organ transplant rejection.

  • Blood transfusion reaction.

  • Extracorporeal circulatory bypass.

  • Acute pancreatitis.


  • Haemorrhage.

  • Respiratory failure due to haemorrhage, haemothorax, or embolism.

  • Acute kidney injury due to microemboli or hypovolaemia.

  • Cerebral ischaemia or infarction due to haemorrhage or thrombus.

  • Gastrointestinal haemorrhage.

  • Small bowel infarction due to mesenteric embolus.

  • Skin petechiae, purpura, bruising, and necrosis resulting from decreased capillary refill and/or infarction.


  • Adequate fluid replacement and restoration of tissue perfusion.

  • Treatment of the underlying cause (e.g. sepsis).

  • Careful monitoring of haemodynamics and arterial blood gases.

  • Observation of endotracheal and nasogastric aspirate, urine, and stool for blood.

  • Observation of the skin and extremities for ischaemia.

  • Regular blood tests, particularly clotting screen, including fibrinogen, thrombin time, and D-dimers.

  • Heparin is not usually given, and blood component transfusions are avoided if there is no active bleeding.

Laboratory values in DIC

  • Prolonged prothrombin time (> 15 s).

  • Prolonged partial thromboplastin time (> 60–90 s).

  • Prolonged thrombin time (> 15–20 s).

  • Low fibrinogen levels (< 75–100 mg/dL).

  • Low platelet count (< 20–75 × 109/L).

  • High levels of fibrin degradation products (> 100 mg/mL).

  • Raised levels of D-dimers.

Note: not all of the results will necessarily be abnormal.


This is a genetic disorder which can cause severe bleeding from minor trauma, and disabling muscle and joint haemorrhages.

  • Haemophilia A is caused by deficiency of factor VIII.

  • Haemophilia B is caused by deficiency of factor IX.


  • Administer factor VIII or IX concentrate (give prophylactically prior to surgery or dental extraction).

  • Aim to raise the factor to above 30% of normal.

  • Repeat infusions every 8–10 h as necessary.

  • Never give aspirin, as this impairs platelet function.

  • Avoid the use of intramuscular injections.

Further reading

Levi M et al. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Journal of Haematology 2009; 145: 24–33.Find this resource:

Richards M et al. Guideline on the use of prophylactic Factor VIII concentrate in children and adults with severe haemophilia A. British Journal of Haematology 2008; 149: 498-507.Find this resource:

Blood components for transfusion

Packed red blood cells

  • Leucocyte depleted as standard.

  • CMV-negative and irradiated on request.

  • Cross-matching is required.

  • Stored at 2–6°C in a dedicated blood fridge.

  • Once removed from the fridge, administer within 30 min or return to storage.

  • Transfuse using a dedicated transfusion giving set, finishing the transfusion within 4 h of removal of the unit from the fridge.

  • Red blood cell transfusion contains no therapeutic amounts of clotting factors or platelets.

  • Transfusion of 1 unit should raise the Hb concentration by 10 g/L.

Packed red blood cells are used in anaemic patients with:

  • chronic, persistent blood loss

  • bone marrow failure

  • major haemorrhage (see Haematology p. [link]).


  • Leucocyte depleted as standard.

  • CMV-negative and irradiated on request.

  • Adult therapeutic dose is pooled from four separate donors or one single apheresis donor.

  • Cross-matching is required.

  • Stored at 22°C under gentle agitation in dedicated storage.

  • Transfuse using a dedicated transfusion giving set within 60 min of out-of-storage time.

Platelets are used in thrombocytopenic patients with:

  • chronic, persistent low platelet counts

  • bone marrow failure

  • immune thrombocytopenia

  • acute DIC (see Haematology p. [link])

  • major haemorrhage (see Haematology p. [link])

  • uraemia.

Fresh frozen plasma (FFP)

  • Leucocyte depleted as standard.

  • Methylene blue on request.

  • Cross-matching is not required.

  • Dose is 12–15 mL/kg.

  • Stored frozen, and once thawed has a shelf life of 24 h.

  • Transfuse full dose using a dedicated transfusion giving set within 4 h.

FFP is used for:

  • replacement of coagulation factor deficiencies where there is no specific factor concentrate available

  • immediate reversal of warfarin in the presence of life-threatening bleeding

  • acute DIC (see Haematology p. [link])

  • thrombotic thrombocytopenic purpura

  • plasma exchange

  • advanced liver disease (see Haematology p. [link])

  • major haemorrhage (see Haematology p. [link]).


  • Leucocyte depleted as standard.

  • Cross-matching is not required.

  • Contains factor VIII, fibronectin, and fibrinogen.

Cryoprecipitate is used to provide replacement factors in patients with:

  • haemophilia or von Willebrand’s disease

  • major bleeding associated with hypofibrinogenaemia (< 1 g/L) or uraemia

  • acute DIC (see Haematology p. [link])

  • advanced liver disease (see Haematology p. [link])

  • bleeding associated with thrombolytic therapy

  • major haemorrhage (see Haematology p. [link]).

Blood transfusion complications

Transfusion reactions due to allergens, bacteria, or incompatible blood usually occur within 10–15 min of starting the transfusion. Monitoring (including haemodynamics and temperature) is essential throughout this period. Correct identification of the patient at the sampling and administration stage will prevent significant errors and harm to the patient.

Febrile non-haemolytic reactions


  • Incompatibility of donor red cells, white cells, platelets, or plasma proteins.

  • Anti-HLA (human lymphocyte antibodies), granulocyte-specific, and platelet-specific antibodies in the recipient as a result of sensitization during pregnancy or previous transfusions.


  • Pyrexia.

  • Urticaria.

  • Pruritus.


  • Antipyretics (aspirin, paracetamol).

  • Antihistamines (e.g. chlorphenamine).

  • Hydrocortisone.

  • Continue the transfusion slowly if there is only a mild reaction.

  • Stop the transfusion if rigors or fever > 38°C occur.

  • Send the implicated unit to the laboratory for examination.

Acute haemolytic reactions


  • Incompatible ABO blood group.

  • Incorrectly stored blood.

  • Out-of-date blood.

  • Overheated blood.

  • Infected blood.

  • Mechanical destruction of the red cells due to administering the infusion under pressure.

  • Mixing of blood with hypotonic infusion fluids.


  • Pain at the infusion site.

  • Pyrexia, facial flushing, rigors, nausea, and vomiting.

  • Dyspnoea.

  • Headache, chest, abdominal, and loin pain.

  • Tachycardia and hypotension leading to circulatory collapse.

  • Oliguria and renal failure.

  • DIC.


  • Stop the blood transfusion immediately.

  • Retain the unit and return it to the laboratory with samples to check the blood group, FBC, coagulation screen, fibrinogen, U&E, and direct antiglobulin test.

  • Take blood cultures if sepsis is suspected.

  • Take a urine sample for haemoglobinuria.

  • Resuscitative measures, including mechanical ventilation.

  • Continuous cardiovascular monitoring.

  • 12-lead ECG.

  • Maintain urine output at > 1 mL/kg/h.

  • If DIC develops, clotting factor replacement may be required.

  • Provide renal support if acute kidney injury develops.

Circulatory overload

Patients are less able to tolerate the fluid load associated with blood transfusion, and can develop pulmonary oedema and heart failure. The evidence suggests that overload can occur with transfusion volumes of as little as 1 unit (median volume of transfusion is 2 units).


  • Dyspnoea or tachypnoea.

  • Hypertension.

  • Elevated jugular venous pressure.

  • Tachycardia.


  • Continuous cardiovascular monitoring.

  • Diuretics.

  • Respiratory support, including non-invasive ventilation.

  • Avoid circulatory overload by administering diuretic at the beginning of the transfusion.

Transfusion-related acute lung injury (TRALI)

This is associated with leucocyte antibodies present in donor blood reacting with recipient white blood cells. Clinical features typically occur within 1–2 h of transfusion, and include chills, fever, non-productive cough, dyspnoea, cyanosis, hypotension that is unresponsive to fluid challenge (10–15%), or hypertension (15%). Radiological signs include bilateral pulmonary infiltrates and scattered opacities.

Transfusion-associated graft versus host disease

This condition is rare, but usually fatal. It is caused by engraftment of viable T lymphocytes, which cause widespread tissue damage. It can occur in immunosuppressed patients (e.g. bone marrow transplant recipients). It can be prevented by irradiating blood products (red cells, platelets, and white cells) prior to transfusion.

Blood transfusion hazards

Bacterial contamination

Contamination of blood is rare, but may be lethal. Contaminants from the donor’s skin can enter the blood during donation. Gram-negative bacteria grow slowly at 4°C, but their growth accelerates at room temperature. Onset of pyrexia and circulatory collapse can be rapid. Failure to maintain aseptic technique in the setting up of the transfusion is another contamination hazard.

Transmission of disease

Donor selection criteria and testing of donor blood for infectious agents have decreased transmission of disease, but have not completely eradicated it.

Diseases that may potentially be transmitted include:

  • hepatitis B and C

  • cytomegalovirus (CMV)

  • malaria

  • HIV.

Hazards of massive blood transfusion

Massive blood transfusion is defined as the transfusion of the patient’s own volume of blood within a 24-h period.


  • Transfused red cells can rapidly cool the patient. Use a thermostatically controlled blood warmer if giving more than several units of blood to a normothermic patient.

  • Hypothermia increases the risk of cardiac arrhythmias, reduces the rate of metabolism, and shifts the oxygen dissociation curve to the left.

  • Citrate toxicity is more likely to occur if the patient is hypothermic.

Acid–base and electrolyte disturbances

  • Stored blood is acidic (pH 6.6–6.8) due to the citric acid that is used as an anticoagulant and the lactic acid that is generated during storage. Both are metabolized by the liver in the well-perfused patient, but may cause a metabolic acidosis in the hypoperfused patient or the patient with liver failure. Monitor with regular acid–base measurements.

  • The sodium content of FFP is higher than that of normal blood due to the sodium citrate anticoagulant. Monitor Na+ levels (particularly in patients with renal failure and hypernatraemia).


  • Stored red cells contain anticoagulants such as citrate that can cause calcium depletion. Monitor ionized calcium levels and give supplements as necessary.

  • Observe the patient for tetany, muscle tremors, cardiac dysfunction, and prolonged QT interval on ECG.

Further reading

Contreras M (ed.). ABC of Transfusion, 4th edn. Wiley-Blackwell: Chichester, 2009.Find this resource:

McClelland D. Handbook of Transfusion Medicine. 5th edn. TSO: London, 2013.Find this resource:

Serious Hazards of Transfusion (SHOT).