Urine microscopy may show leucocytes ( > 100/mL correlates well with infection, but may be due to contamination or other urinary tract pathology). RBCs are commonly seen on microscop y, but in isolation have a low degree of sensitivity or speci \201 city for UTI. Underlyin g renal pathology is suggested by \201 nding urinary crystals, RBC, or granular casts. MSU for culture and sensitivity. Transportation the sample to the laboratory without delay to ensure that bacterial overgrowth does not arti \201 cially i the count. Dipslides dippe d into freshly passed urine and transported in a plastic container to the laboratory are an alternative. 159 URINARY TRACT INFECTION Treatment \200 It is usually reasonable to discharge female patients with uncomplicated l ower UTIs with antibiotics . Commence a 3 \200\2236 day course of trimetho- prim or nitrofu rantoin. Provide advice regarding \202 uid intake, no \200\230holding on \200\231, and v oiding after intercourse. Drinking barley water is as effective as attempts at urinary alka linization with sodium bicarbonate. ( Note: urinary alkalinization renders nitrofurantoin i neffective). Advise the patient to see her GP for review, MSU result, and repeat MSU. Elderly men and women with asymptomatic bacteriuria should not receive antibiotic treatment unless they show signs of being unwell. \200 In pregnancy, both symptomatic and asymptom atic bacteriuria should be treated with an antibiotic such as amoxicillin. Given the dif \201 culty in distinguishing prostatitis from simple UTI in men, they should receive a 2-week course of cipro \202 oxacin, trimethoprim, or co-amoxiclav. Arrange GP f ollow-up. Treat catheterized patients with symptoms or signs of UTI for 7 days with cipro \202 oxaci n or co-amoxiclav. Treatment is more effective if the catheter is changed in the ED prior t o commencing antibiotics. Do not treat catheterized patients with asymptomatic bacteriuria with antibiotics. Refer for investigation and treatment all male patients and females with recurrent infectio ns, pregnancy, GU malformation, immunosuppression, or renal impairment. Patients with acute pyelonephritis usually require admission for parenteral antibiotics, \202 uid replacement, and analgesia. Assess and treat for severe sepsis ( b Shock, p.60). See http://www.sign.ac.uk 160 CHAPTER 3 Medicine Chronic renal failure Patients with established chronic renal failure (CRF) are likely to b e very well known to the hospital. Obtain old notes and recent blood results, and liaise ea rly with in-patient specialist teams. Established chronic renal failure (not on dialysis) Patients with mild CRF (glomerular in \201 ltration rate (GFR) > 40mL/min \200\224 100mL/min) are unlikely to have speci \201 c problems related to their underlying renal failure. With GFR <40mL/min, and especially if GFR <10mL/min, complications may in \202 uence presentation and treatment. These patients are prone to pathological fractures. Secondary hyperparathyroidism and osteomalacia (lack of active vitamin D) occur in moderate GFR. In severe CRF, aluminum bone disease, and B 2 - microglobulin related amyloidosis may be associated with pathological fractures. \200\230Pseudo-gout \200\231 due to high Ca 2 + /PO 4 \200\223 production and twitching/tetany due to hypocalcaemia may occur. Other problems include: Defective regulation of extra-cellular \202 uid volume There is a n i risk of \202 uid depletion in moderate CRF and \202 uid retention in severe CRF. Hi gh dose diuretics may be required in severe disease: the combination of furosemide and meto lazone may be effective even with very low GFRs. Hyperkalaemia Most patients preserve potassium balance, but cannot deal with sudden K + loa ds (eg dietary, tissue damage/catabolism, GI bleed). Associated d Ca 2 + compounds the card iac effects. Plasma K + may i very quickly, so monitor ECG and check K + frequently. Hypert ension Often severe and resistant, with an i incidence of accelerated phase. Ciclosporin an d erythropoietin i BP, and can precipitate hypertensive encephalopathy. Drug effects Drugs may accumulate (eg opioids, acyclovir, some antibiotics), worsen renal f ailure (eg NSAIDs, ACE inhibitors, which d renal perfusion), cause hyperkalaemia (eg K + sp aring diuretics, ACE inhibitors, NSAIDs). Infections Impaired WBC function, with i risk of severe infection and features of infection (eg pain, fever) may be masked by the relative i mmuno-compromised state. Bleeding Platelet function is impaired. Pericarditis A sign of severe CRF, indicating the need for dialysis. Neurological dysfunction Usually a sign of severe uraemia \200\224 convulsions and/or alte red conscious state indicate a global metabolic disturbance. 161 CHRONIC RENAL FAILURE Common emergency presentation in haemodialysis patients Pulmonary oedema Usually occurs sho rtly before the next dialysis session and may re \202 ect \202 uid overload due to non-c ompliance with diet and \202 uid restriction. Most are virtually anuric, so diuretics are ineffective. Get the patient on dialysis without delay. While this is being arranged give high \202 ow O 2 and SL buccal or IV nitrates. Pre-dialysis hyperkalaemia May present wit h neuromuscular symptoms (eg muscle spasms, weakness, paralysis, paraesthesiae) or arrhythm ias, including cardiac arrest. Standard treatment ( b p.162) can buy time while emergency d ialysis is arranged. When giving glucose/insulin, give 6U of insulin at most (there is a ri sk of late hypoglycaemia, since insulin half-life will be i ). Complications of vascular ac cess Arteriovenous \201 stulae are a dialysis patient \200\231s lifeline \200\224 never occlude limb with BP cuffs or tourniquets. Do not use for vascular access unless life-threa tening emergency. Acute shunt thrombosis (loss of palpable thrill, often local pain/redness ) is a vascular emergency. Arteriovenous \201 stulae and central lines are common infecti on sources (usually staphylococcal), often with no overt external abnormality, but presenti ng with acute \200\230viral illness \200\231 symptoms. Continuous ambulatory peritoneal dialysis Bacterial peritonitis Occurs every 12 \200\22318 patient-months. Features are cloudy drained dialysate bags, abdominal pain, and peritonism. Systemic sepsis is usually absent or minimal. Staphylococci are most common organisms. Sus pect underlying surgical cause (most often diverticular abscess) if Gram \200\223ve organi sms or anaerobes present in drainage \202 uid, and particularly if > 1 type of organism i s found on microscopy or culture. Diabetic patients on continuous ambulatory peritoneal dialysis can develop acute severe (us ually non-ketotic) hyperglycaemia , related to high dialysate glucose concentrations (80 \200\223140mmol/L). Hernias of all types, leakage of dialysate into the abdominal wall or the pleural cavity, a nd scrotal swelling (open processus vaginalis) may occur. Transplant patients Contact the transplant team whenever any transplant patient presents to the ED. They will know the patient well and will advise about drug therapy, intercurrent p roblems, and help with follow-up. Acute rejection Signs include pain, tenderness, and swelling over graft, d urine output, fe ver, systemic upset, biochemical deterioration. Often indistinguis\hable from acute bacteri al infection: if in doubt treat for both, pending results of further testing by specialists (renal biopsy, blood, and urine cultures). Infections May be opportunist, whilst \200\230conventional \200\231 infections are unduly severe, with response modulated by steroids. Poor wound healing, avascular necrosis and pathological fractures May be caused by steroids . 162 CHAPTER 3 Medicine Hyperkalaemia Hyperkalaemia is classi \201 ed as mild (K + 5.5 \200\2236.0mmol/L), moderat e (K + 6.1 \200\2236.9mmol/L) or severe (K + > 7.0mmol/L). Causes Spurious Sample haemolysed or taken from limb with IVI containing K + . d Renal excr etion Acute kidney injury, patients with chronic renal failure or on dialysis with K + load , K + sparing diuretics (eg spironolactone, amiloride). Cell injury Crush injury and other causes of rhabdomyolysis, burns, tumor cell necrosis, massive, or incompatible blood transf usion. K + cellular shifts Acidosis from any cause (eg DKA), drugs (suxamethonium, B-blocke rs). Hypoaldosteronism Addison \200\231s disease, drug-induced (NSAIDs, ACE inhibitors). Clinical features There may be muscle weakness/cramps, paraesthesiae, hypotonia, focal neur ological de \201 cits. Dangerous hyperkalaemia may be asymptomatic. ECG changes ECG changes typically progress as hyperkalaemia worsens as follows: \200 Peak ed T waves. \200 Small, broad, or absent P waves. \200 Widening QRS complex. \200 Sin usoidal ( \200\230sine wave \200\231 pattern) QRST. \200 AV dissociation or VT/VF. Management of severe hyperkalaemia Urgent treatment is needed if K + > 6.5mmol/L, unless th is is a spurious and incorrect result. If K + is reported as > 6.5mmol/L obtain venous acce ss, monitor and review the ECG. Start treatment immediately (as indicated below) if there a re ECG changes of hyperkalaemia. If there are no ECG signs of hyperkalaemia take another bl ood sample for U&E, with care to avoid haemolysis, and a heparinized sample to measure K + on a blood gas machine: \200 Give 10mL of 10 % calcium chloride slowly IV (over 5min). Th is does not lower K + , but antagonizes cardiac membrane excitability. Hypercalcaemia may p ossibly potentiate toxicity in patients on digoxin, so give as an IVI over 30min in these p atients. Give 10U of short-acting human soluble insulin with 50mL of 50 % glucose IV. This helps i c ellular uptake of K + , lowering serum levels by up to 1mmol/L within 1hr. Give 5mg nebulized salbutamol, repeated once as necessary. This will lower K + in most patients, acting in 8 30min. Correct volume de \201 cits/acidosis with IV \202 uids and isotonic (1.26 % ) sodium bic arbonate or aliquots (25 \200\22350mL) of 8.4 % . Beware \202 uid over- load/osmolar effe cts, especially in dialysis patients. Correct the underlying cause if possible (eg steroid therapy for Addison \200\231s disease). Contact the nephrology team urgently for patients with acute or chronic renal failure as emergency dialysis may be needed. Hyperkalaemia in children \200\224 see b Renal failure, p.694. 163 HYPERKALAEMIA Management of hyperkalaemic cardiac arrest If a patient in cardiac arrest is known to have hyperkalaemia, follow the standard ALS guidelines ( b p.46), plus one or more of the follow ing: \200 Give 10mL of 10 % calcium chloride IV by rapid bolus injection. \200 Consider giving 10U of short-acting insulin + 100mL 50 % glucose rapidly IV. If there is severe acidosis, give 50mL 8.4 % sodium bicarbonate rapidly IV. \200 Consider haemodialysis for cardiac arrest induced by hyperkalaemia which is resistant to medical treatment. Management of moderate hyperkalaemia Provided that the result is not spurious, a K + of 6 \200\2236.5mmol/L may be regarded as \200\230moderately \200\231 severe hyperkalaemia. \200 Obtain venous access and monitor ECG. \200 If there are ECG changes, treat as for s evere elevation opposite. \200 If there are no ECG changes, give 10U of short-acting huma n soluble insulin with 50mL of 50 % glucose IV over 15 \200\22330min. Look for and treat the underlying cause and consider: diuretics (eg furosemide 1mg/kg IV slowly) and dialysis. Management of mild hyperkalaemia K + of 5.5 \200\2236mmol/L. Treat the underlying cause and treat any associated hypovolaemia. Discuss need for speci \201 c intervention (diuretic, dialysis) with the medical team. 164 CHAPTER 3 Medicine Hypokalaemia De \201 ned as K + <3.5mmol/L, it is relatively common. Moderate hypoka- laem ia may result in lethargy, weakness, and leg cramps. In severe cases (K + <2.5mmol/L), rhab domyolysis and respiratory dif \201 culties may occur. ECG changes include prominent U wav es and \202 attened T waves. Treatment In most instances, aim to replace potassium gradually. The maximum recommended IV infusion rate of potassium is 20mmol/hr. Restrict more rapid rates of IV infusion (eg 20mm ol in 20 \200\22330min) to those patients who have unstable arrhythmias when cardiac arrest is imminent (obtain senior/expert advice). Ensure cardiac monitoring occurs during any pot assium IVI. Associated magnesium de \201 ciency Many patients with potassium de \201 ciency are also magnesium de \201 cient. Consider replacing magnesium in those patients who have severe hy pokalaemia. See also www.resus.org.uk 165 PORPHYRIA Porphyria The porphyrias are haem biosynthesis disorders in which enzyme de \201 ciencies cause accumulation of porphyrin and porphyrin precursors. Most cases are hereditary, but ab normal porphyrin metabolism may develop in iron de \201 ciency, alcohol excess and lead po isoning. The acute porphyrias (acute intermittent porphyria, variegate porphyria and heredi - tary coproporphyria) affect 8 1 in 10,000 people in the UK. The non-acute porphyrias (eg porphyria cutanea tarda) do not produce acute attacks, but cause skin photosensitivity some times associated with liver disease. Attacks of acute porphyria are often caused by drugs: barbiturates, oestrogens, progesteron es, sulphonamides, methyldopa, carbamazepine, phenytoin, sulphonylureas, chloramphenicol, t etracyclines, danazol, some antihistamines. Other precipitants include: alcohol, smoking, d ieting, emotional and physical stress, infection, substance misuse, pregnancy. Clinical features of acute porphyria \200 Abdominal pain is common and can be severe, wit h nausea, vomiting and constipation. Abdominal examination may be normal or there may be mi ld generalized tenderness. Peripheral neuropathy is usually motor, rather than sensory, and may progress to paralysis and respiratory failure. Tachycardia, hypertension, and postural hypotension. \200 Psychiatric manifestations: agi tation, depression, mania and hallucina- tions. Hyponatraemia due to inappropriate ADH secretion can cause \201 ts or coma. Investigation and management of acute porphyria Look for a Medic-Alert bracelet. Obtain old medical notes. If an acute attack is suspected, send a fresh urine sample (protected from light) to test f or amino laevulinic acid and porphobilinogen. In an attack, urine goes dark red or brown, e specially if left exposed to light (due to polymerization of porphobilinogen). Treat acute attacks supportively (if necessary in ICU). Maintain carbohydrate intake (PO or IV). Control mild pain with paracetamol or aspirin; moderate/severe pain with morphine ( anti-emetic). Consider chlorpromazine for agitation; propranolol to control severe hypert ension. Management of status epilepticus is dif \201 cult as many anticonvulsants are cont raindicated: choose IV diazepam in the \201 rst instance. Haem arginate helps some patien ts with acute crises (take specialist advice). Prescribing for patients with porphyria Many drugs can precipitate attacks, so check with t he patient and the BNF . However, the safety of many drugs in porphyria is uncertain and effects vary between patien ts. If in doubt, obtain specialist advice. In addition to those mentioned earlier, safe dru gs appear to be: ibuprofen, penicillin, cipro \202 oxacin, bupivicaine. Data is also available on the internet at www.uq.edu.au/porphyria 166 CHAPTER 3 Medicine Bleeding disorders: 1 Contact a hematologist whenever treating a patient with a known or su spected bleeding disorder Haemostasis requires co-ordination between the vascular system, p latelets and coagulation pathways to limit blood loss from the circulation. Platelets inter act with vascular subendothelium, forming a primary platelet plug, which is strengthened by cross-linked \201 brin strands formed via the coagu- lation cascade to allow restoration of vascular integrity (see Fig. 3.24 ). The \201 brinolytic systems prevent excess clot formation, and inappropriate local or generalized thrombosis, by promoting lysis of \201 brin. Recognition of bleeding Bleeding is expected after trauma, but suspect a bleeding disorder if spon- taneous or excess hemorrhage occurs from multiple or uninjured sites, into deep ti ssues, joints or delayed bleeding occurs (hr/day). Bleeding dis- orders may be congenital o r acquired. Ask about previous bleeding after trauma, dentistry or surgery and the family h istory. Congenital disorders Hemophilia A (Factor VIII de \201 ciency), Hemophilia B (Factor IX de \201 ciency), and von Willebrand \200\231s disease. Most adults with a congenital disorde r know the nature of it and carry a National Hemophilia card or Medic-Alert bracelet giving details. Many hemophiliacs know more about their required treatment than you! They will be registered and known at a hemophilia center. Acquired disorders May be due to liver disease, uraemia, drug use (ask speci \201 cally ab out aspirin, NSAIDs, warfarin/anticoagulants, alcohol), or unrecognized conditions such as hematological malignancy. Hypothermia ( b p.254) from whatever cause aggravates any bleedin g tendency. For example, an INR assay performed at 32 C will be prolonged to the same ex tent as would occur with a Factor IX level of 2.5 % of normal. The severity of this may not be recognized merely from standard tests as these are performed at 37 C. The site of bleeding can give a clue as to the abnormality. Platelet problems (usually thro mbocytopenia) often present with mucocutaneous bleeding (eg epistaxis, GI, GU, or heavy men strual bleeding, bruising, purpura, and petechial hemorrhages). Bleeding into joints or pot ential spaces (eg retroperitoneal) and delayed bleeding is more often due to coagulation fa ctor de \201 ciencies. Patients with mucocutaneous bleeding and hemorrhage into deep space s may have a combined platelet and coagulation factor abnormality (eg disseminated intravas cular coagulation (DIC)). 167 BLEEDING DISORDERS: 1 Investigations FBC Remember that in acute bleeds, Hb and Hct values fail to demonstrate the severity of red cell loss as haemodilution takes time. Platelet counts <100 \227 10 9 /L indicate thrombocytopenia, and <20 \227 10 9 /L are associated with a risk of spontaneous bleeding. Bleeding because of platelet problems can occur with \200\230normal \200\231 cou nts if platelet function is abnormal (eg with aspirin or clopidogrel). Prothrombin time (INR) Used to monitor anticoagulant control in patients on coumarin drugs and may be prolonged in liver disease. Activated partial thromboplastin time (APTT) Tests components of intrinsic and common coagu lation pathways (essentially all factors except VII and XIII). Individual factor levels Can be determined by speci \201 c assays together with inhibitor screening tests for antibodies that can prolong normal plasma clotting. Vessel injury Collagen exposure Tissue factor Platelet release reaction Serotonin Platelet phospholipid Blood coagulation cascade Vasoconstriction Thromboxane A2, ADP Platelet aggregation Primary haemostatic plug Reduced blood flow Thrombin Platelet fusion Stable haemostatic plug Fibrin Fig. 3.24 Reactions involved in haemostasis. 168 CHAPTER 3 Medicine Bleeding disorders: 2 General aspects of treatment \200 Perform routine wound/fracture ma nagement of patients with bleeding disorders, but consider need for prior or simultanous ad ministration of factor concentrates/platelets under hematological guidance. Spontaneous or traumatic bleeding into the neck or pharynx may cause rapid airway compromise. Always consider intracranial hemorrhage in a patient with headache, neurological symptoms o r minor head trauma. Consult to consider need for commencing treatment before speci \201 c investigation (eg CT). Never give IM injections. \200 Do not attempt central line placement except in extremis, since life- threatening, uncontrollable bleeding can result. Before giving any drug, check whether it may aggravate the condition or interfere with intercurrent therapy. Speci \201 c conditions Vascular lesions May be inherited (Ehlers \200\223Danlos syndrome, pseudo- xanthoma elasticum, osteogenesis imperfecta, haemorrhagic telangiectasia) or acqui red (eg due to steroids, infection e.g. meningococcaemia, thrombotic thrombocytopenic purpu ra, vasculitis, scurvy). Platelet disorders Capillary-related mucocutaneous bleeding is com mon and may occur immediately after injury/surgery (eg dental extractions). The platelet co unt may be normal or d . Acquired thrombocytopenia may be due to drugs, toxins, infections, autoimmune conditions (eg ITP), DIC, or to massive blood transfusion. Abnormal platelet fu nction occurs with uraemia, myeloproliferative disorders, and drugs (eg aspirin). Coagulati on pathway disorders Congenital coagulation pathway disorders predominate in males. They ca use intramuscular or deep soft tissue haematomas. Bleeding onset after injury/surgery may b e delayed 2 \200\2233 days. von Willebrand \200\231s Disease The commonest congenital bleed ing disorder, with VW Factor and Factor VIII de \201 ciency, and abnormal platelet functio n. Clinically, the condition is similar to a platelet disorder, but milder. Bleeding is com monly mucosal (eg epistaxis) and usually treated with Factor VIII concentrate (which includ es VW Factor). Hemophilia A Caused by a lack of functional factor VIII which is needed for clot formation. Often presents with bleeding into deep muscles, large joints or urinary tra ct. Intracranial bleeding is a major cause of death at all ages. Anticipate bleeding up to 3 days after trauma. In UK, hemophilia A associated with bleeding or potential bleeding is normally treated by Factor VIII concentrate (some patients have \200\230home supplies \200 \231 and may bring them to hospital). The volume (dose) depends upon the severity of the he mophilia of the individual patient and the purpose of treatment (ie prophylaxis or therapy for current bleeding). Hemophilia B (Christmas disease) Involves a de \201 ciency of Facto r IX activity and is genetically and clinically indistinguishable from hemophilia A, but mu ch less common. It is normally treated with factor IX concentrate. 169 BLEEDING DISORDERS: 2 Disseminated intravascular coagulation (DIC) Patients may present with DIC due to infection (especially Gram \200\223ve sepsis), trauma, malignancy, pregnancy (amniotic \202 uid e mbolism, placental abruption, toxemia, retained products), any cause of shock, incompatible blood transfusion or massive volume replacement. Following triggering of the coagulation p rocess, consumption of platelets, and coagulation factors (particularly \201 brinogen, V, VIII, and XIII) occurs with thrombin formation overwhelming the normal inhibition system, resulting in systemic \201 brin dep- osition (Fig. 3.25 ). Activation of the \201 brino lytic system results in dissolution of \201 brin and release of \201 brin degradation p roducts. Investigations Platelet count is usually d , INR i and APTT i , \201 brinogen le vel d , \201 brin degradation products i . Treatment Is complex and requires control of t he primary cause of the DIC to avoid total depletion of clotting factors. Obtain expert adv ice about replacement therapy with platelets, FFP, prothrombin complex concentrate, heparin and blood (particularly required if the patient is actively bleeding). EXTRINSIC SYSTEM INTRINSIC SYSTEM XII (on contact with vascular endothelium) XIIa Tissue factor +VIII +Ca2+ XI XIa IX Xa +VIII +Ca2+ +Phospholipid X Xa +V +Ca2+ +Phospholipid XIII Prothrombin Thrombin XIIIa Cross linking Fibrin Fibrinogen Fig. 3.25 Coagulation cascade. 170 CHAPTER 3 Medicine Patients on anticoagulants The commonest oral anticoagulant is warfarin sodium, a vitamin K antago- nist. This inhibits the production of Factors II (prothrombin), VII, IX and X ande d plasma levels of these factors. Patients, or their relatives, who are able to give a his tory will usually know if they are taking warfarin, and their most recent prothrombin time or INR test result, together with any changes in treatment. If this history is not available, suspect patients with prosthetic heart valves, mitral val ve disease, AF, a past history of DVT/PE or TIAs to be on anticoagulants. Intercurrent illn ess, liver disease and changes in diet, and/or alcohol consumption may affect anticoagulant control. Concurrent drug administration with unrecognized potential for interaction is the commonest cause for acute changes in anticoagulant control. These patients usually present with one of three problems. Acute hemorrhage Spontaneous bleeding in patients on warfarin most commonly affects the GI tract, GU tract, joints, or muscles. After injury, expect excessive or continuing bleeding. Anticipate the i risks of occult or unrecognized bleeding (eg intraperitoneally or intracr anially) after even minor trauma and maintain a high index of suspicion as to these possibi lities. Check INR and FBC in all patients. Other investigations (eg CT scan of head/abdomen, USS) w ill be dictated by the nature of the acute problem. Patients with life-threatening hemorrhage For patients with life-threatening hemorrhage, co mmence volume replacement and blood transfusion as appropriate (see b Blood trans- fusion 1 , p.172). Contact hematology for specialist advice which may include phytomenadione (vitami n K 1 ) up to 10mg by slow IV injection and provision of prothrombin complex concentrate. Patients with less severe hemorrhage Patients with muscle haematomas, haematuria, or epista xis also require hospital admission for observation and speci \201 c local treatment. Stop war- farin therapy for one or more days. Phytomenadione 0.5 \200\2232mg by slow IV injecti on may be advised by the hematologists. Note that vitamin K 1 can interfere with warfariniz ation for several days, so take expert advice when the patient is also at high risk of thro mbosis (prosthetic heart valve). INR levels within the therapeutic range Patients who develop bleeding with INR levels withi n the therapeutic range require investigation of a possible underlying cause (eg GI or GU t ract pathology). See http://www.bcshguidelines.com 171 PATIENTS ON ANTICOAGULANTS Check of control of anticoagulation The therapeutic range for the INR may vary according to the indication for anticoagulation. An INR of 2.0 \200\2233.0 is usually appropriate for D VT prophy- laxis and 3.0 \200\2234.0 for patients with mechanical prosthetic heart valves. For patients who have INR 4.0 \200\2237.0 without hemorrhage, withhold warfarin therapy for 1 or 2 days, and arrange review by appropriate specialist team or GP. For patients with IN R > 7.0 without hemorrhage, withhold warfarin and obtain specialist consultation before con sidering phytomenadione (vitamin K 1 ) 5mg by slow IV injection or orally. Interactions with other prescribed or proprietary medicines Many drugs can interfere with a nticoagulant control. Before giving or stopping any drug in a patient taking warfarin or ot her anticoagulant, check the potential for interaction \200\224 Appendix I in the BNF . Particular groups of drugs, likely to be prescribed in the ED, which may cause problems inc lude analgesics (especially NSAIDs), antibacterials and anti-epileptics. Always LOOK IT UP. Other oral anticoagulants Dabigatran (a direct thrombin inhibitor) and rivaroxaban (a Facto r Xa inhibitor) are among a group of new oral anticoagulants which may be prescribed instea d of warfarin or low molecular weight heparin, in certain conditions. They do not require r outine blood monitoring. To date, there are no guidelines for measuring their effect in pat ients who are bleeding, and there is no proven way to reverse their effect. Always discuss bleeding patients on new oral anticoagulants with a hematologist. Attempts at reversal may include FFP or prothrombin complex concentrate. 172 CHAPTER 3 Medicine Blood transfusion 1 It is better to stop bleeding than to have to replace blood loss General aspects Correctly documenting and labeling blood tubes and forms, combined with che cking blood products prior to administration, is crucial for safe patient care. If a patien t \200\231s name(s), date of birth, clinical details and address are unknown or uncertain, identify them for transfusion purposes by a unique number (usually their unique ED number) and inform the blood transfusion laboratory. To avoid confusion, the doctor taking the blood sample must label and sign the tube at the patient \200\231s bedside, complete the form, and contact the transfusion service. Only tak e blood from one patient at a time. Label tubes immediately to minimize the risk of mislabe lling. Blood banks may refuse to handle incorrectly labeled forms/tubes. If you knowingly give a blood product (or animal product e.g. gelatin) to a patient whom yo u know would not accept this (eg a Jehovah \200\231s Witness) you are likely to face an ind efensible medicolegal claim. What to send 10mL clotted blood is usually adequate for adults. Where it is obvious that ma ssive transfusion may be required, send two 10mL samples. On the request form, indicate how much blood is needed, when and where the blood is to be sent. Date and sign the form. What to request The amount of blood to be delivered and to be kept available at the transfu sion center for immediate dispatch depends on the patient \200\231s clinical state and asse ssment of future blood losses. Assessment of a patient with hypovolaemic shock is complex a nd includes recognition of the clinical situation, the potential blood loss, together with a current assessment of the patient and investigations. Hb and Hct values may be misleading . It may take hours for their values to equilibrate to those indicating the degree of blood loss. Group and screen The patient \200\231s ABO and Rhesus D group is determined and the serum t ested for unexpected red cell antibodies. Subsequently, if required, blood can be provided within 10 \200\22315min, assuming the antibody screen is clear. Request \200\230Group and screen \200\231 where a patient does not need transfusion in the ED, but may require it lat er. Cross-match Full blood compatibility testing may take up to 1hr. If blood is required more urgently, ABO and Rh compatible units can usually be provided within 15min, including an \200\230immediate spin cross-match \200\231 as a \201 nal check on ABO compatibility. In exsanguinating hemorrhage, uncross- matched group O Rhesus \200\223ve blood can be issued immediately. 173 BLOOD TRANSFUSION 1 Blood products The UK uses blood component therapy. There appears to be no speci \201 c ad vantage in using \200\230whole \200\231 blood as opposed to red cells plus a volume expand er. Red cells (additive solution) Each pack (volume 300mL) is from a single donor and has a Hct of 0.65 \200\2230.75 (0.55 \200\2230.65 for RBCs in additive solution). A transfusion of 4 mL/kg will i circulating Hb by 81g/dL. Whole blood A \200\230unit \200\231 contains 530mL (470mL of blood from a single donor + 63mL preservative solution), with a Hct of 0.35 \200 \2230.45. Platelet concentrate either pooled or from a single donor by platelet pheresis. Fresh frozen plasma contains clotting factors and \201 brinogen. Cryoprecipitate is derived from FFP when it is thawed. It is rich in factor VIII, \201 br inogen, and von Willebrand Factor. Prothrombin complex concentrate is a combination of vitamin K dependent Factors II, VII, IX and X. Use PCC to reverse warfarin. Transfusion precautions (UK Blood Safety & Quality Regulations 2005) \200 2 practitioners must con \201 rm all the following steps before commencing transfusion. If there is ANY discrepancy, DO NOT transfuse. Con \201 rm the details on the traceability label on the blood component match the patient \200\231s full name, date of birth, and hospital number (wrist band if unconscious). Check that the traceability label is attached to the blood bag. \200 Ensure the donation number, the patient \200\231s blood group/RhD type all match and that any special requirements are covered. Check every component before starting transfusion for signs of discol- ouration, leaks, clots etc. and the expiry date. If all checks are satisfactory, the 2 practitioners should ensure that the component has be en prescribed (prescription form and/or \202 uid balance chart) and sign the front of the traceability label before commencing the transfusion. Infuse all components through a giving set with integral \201 lter to trap large aggregat es. Microaggregate \201 lters are not routinely required. Never add any drug to a blood component infusion. \200 Do not use giving-sets which previ ously contained glucose or gelatin. \200 Red cell concentrates may be diluted with 0.9 % saline using a Y giving- set to improve \202 ow rates. Never add any other solution. Use a blood warmer, especially for large and/or rapid transfusions. \200 Once the transfu sion has started, peel off the portion of the signed label and attach to the appropriate place in the \202 uid balance sheet. \200 Sign the prescr iption form to con \201 rm the patient identity checks. \200 Complete and sign the label and return it to the laboratory. See: www.transfusionguidelines.org.uk 174 CHAPTER 3 Medicine Blood transfusion 2 Massive transfusion Loss of 50 % of circulating blood volume within 3hr is perhaps the most relevant ED de \201 nition. Resuscitation requires an interdisciplina ry team and clear organization. In the event of massive blood loss \200 Protect the airway and give high \202 ow O 2 . \200 Get help \200\224 two nurses and a senior doctor. \200 Insert two large bore cann ulae and start IV warm saline 1000mL stat. \200 Take FBC, U&E, LFTs, coagulation, and cro ss-match. Label the blood tubes and ensure they are sent directly to the laboratory. Do not leave them unlabelled or lying around in the resusitation room. Telephone the hematology laboratory to warn of potential massive transfusion. Request ABO g roup-speci \201 c red cells if the patient is peri- arrest. This will take only 10min in t he laboratory. Otherwise, request full cross-match and give number of units required. Accurate patient ID is essential, even if the patient is unknown. \200 Call appropriate s enior surgeon \200\224 to stop bleeding as soon as possible. \200 Start blood transfusio n if the patient remains tachycardic and/or hypo- tensive despite crystalloid resuscitation. Repeat all bloods, including FBC, clotting, U&Es, calcium, and magne- sium levels, every hour. Start platelet transfusion if platelet count falls below 75 \227 10 9 /L. \200 Anticipat e the requirement for FFP and consider giving early during the resuscitation. FFP will repl ace clotting factors and \201 brinogen. Aim to maintain \201 brinogen > 1.0g/L and the INR and APTT <1.5 normal. Cryoprecipitate may also be used. Recombinant Factor VIIa might be used as a \200\230last ditch attempt \200\231 to control bleeding in young patients where surgical control of bleeding is not possible, and the abov e has already been corrected. If the drug is available it is usually ordered by a hematolog ist. Massive transfusion complications Rapid infusion of blood products may lead to: Hypothermia Blood products are normally stored at 2 \200\2236 C. Rapid infusion can caus e signi \201 cant hypothermia. Use blood warmers routinely for rapid transfusions (eg > 50 mL/kg/hr or 15mL/kg/hr in children). Never warm a blood product by putting a pack into hot water, on a radiator or any other heat source. Electrolyte disturbances With massive transfusion, the citrate anticoagulant may cause sign i \201 cant toxicity, d plasma Ca 2 + (impairing cardiac function) and acid \200\223base b alance disturbance. This is aggravated in patients with underlying liver disease, hypotensi on or hypothermia. Citrate may also bind Mg 2 + , causing arrhythmias. Prophylactic or rout ine administration of IV calcium salts is not recommended. Monitor ECG and measure ionized plasma Ca 2 + levels during massive transfusion. K + levels i in stored blood and hyperkala emia may follow massive infusion. Routinely monitor the ECG and check plasma K + levels. Tr ansient hypokalaemia may follow 24hr after large volume transfusion 175 BLOOD TRANSFUSION 2 Blood product administration Blood transfusion is not a panacea. An improvement in O 2 deli very cannot be assumed. RBC function deteriorates during storage and changes in O 2 af \201 nity occur withe d 2,3-DPG levels, while d ATP levels alter RBC mem- brane deformabili ty causing i cell stiffness and micro-circulatory problems. UK donations are routinely scre ened for hepatitis B, HIV, HTLV, syphilis, and where necessary, CMV. However, blood cannot be sterilized: small but de \201 nite risks of infection transmission exist. Transfusion reactions Monitor the patient closely for the \201 rst 5 \200\22310min of the infusion of each unit of blood to detect early clinical evidence of acute reactions. If th e patient develops a temperature, shortness of breath, chest or abdom- inal pain or hypoten sion, suspect a transfusion reaction. Treat allergic reactions including itching, urticaria , bronchospasm and fever convention- ally (see b Anaphylaxis treatment, p.43). Mismatched t ransfusion By far the commonest cause is a clerical error when labeling, ordering or admini stering blood. Transfusion of ABO incompatible blood causes acute severe haemolysis and cir culatory collapse. In a hypovolaemic, shocked, or anesthetized patient these features may b e obscured and missed. If a transfusion reaction is suspected: ABO incompatability, haemolytic reaction, bacterial infection, severe allergic reaction, or transfusion-related acute lung injury: \200 Stop the transfusion. \200 Keep the IV lin e open with 0.9 % saline. \200 Record all observations, give supplemental oxygen. \200 Double-check the blood unit label with the patient \200\231s wrist identity band and other identi \201 ers. Send the unit of blood product and the giving set to the blood bank. \200 Take 40mL of bl ood. Send it as follows: 5mL anticoagulated and 5mL clotted blood to blood bank; \200 10mL for U&E; \200 10mL fo r coagulation screening; \200 10mL for blood cultures. Contact the blood bank directly by phone. \200 Contact hematologist directly. \200 Give broad spectrum antibiotic if infection suspected . \200 Monitor \202 uid balance and u rinary output. 176 CHAPTER 3 Medicine Sickle cell disease Sickle cell disease occurs in African, Indian, Middle Eastern, Caribbea n, USA, and Mediterranean populations. It is caused by a genetic mutation in one of the cha ins of the Hb molecule. The normal adult Hb genotype AA produces HbA. In heterozygotes (sic kle cell trait) one gene is abnormal (HbAS) and about 40 % of the patient \200\231s Hb will be HbS. In homozygotes (sickle cell anemia), both genes are abnormal (SS) and > 80 % of th e Hb will be HbS. HbS molecules polymerize in deoxygenated or acidotic con- ditions, causin g RBC sickling. Sickle cells are rigid and fragile. They may haemolyse, or block small vess els leading to tissue ischaemia, infarction and further sickling (see Fig. 3.26 ). Sickling also occurs with genes coding other analogous amino acid substitutions (eg HbSC and SD dis eases). Clinical features Sickle cell trait causes no disability except during conditions of severe hypoxia (eg sudden depressurization in aircraft, or cardiac arrest).