An approach to the management of bleeding disorders

With Dr Shafqat Inam, Haematology Registrar at Concord Hospital and Royal Prince Alfred Hospital

Introduction Clotting is dependent on functional platelets, coagulation factors and vasoconstriction. The cause of bleeding diathesis is usually multifactorial in hospital patients with problems with anticoagulants, anti- platelets, congenital disorders and platelet disorders most commonly seen. Patients with bleeding diathesis can present with anaemia due to slow bleeding over time, or a sudden significant bleed, such as a gastrointestinal bleed.

When interpreting coagulation studies we need to consider the clinical context. APTT measures therapeutic heparin, PT/INR reflects warfarin therapy; both are for general screens for clotting problems. Platelet count normally is around 150-400 x 10^9/L of blood, but what’s normal also depends in the context.

Case 1 - You are a night intern and have been asked to review a patient that has became hypotensive and tachycardic following a right total hip arthroplasty. He is also becoming anxious and pale. There is a large painful haematoma under the surgical site.

1. You are concerned this is an acute post-operative haemorrhage. What would be your approach to this patient?  Inspect how the patient looks from the end of the bed and check the observation chart for signs of hypovolemic shock  For deteriorating patient, commence resuscitation to stabilise him and conduct rapid investigations in parallel  Escalate care to the orthopedic registrar  For ongoing bleeding, compress the bleeding site for haemostasis and insert 2 large bore cannulas and commence fluid resuscitation  Conduct a history to identify the cause of bleed

2. Outline your assessment approach by the bedside  History: o To assess for the underlying cause of the bleed and complications as result of the bleed o Medication history: . Aspirin/Clopidogrel for the prevention of IHD and stroke . Warfarin and Novel Oral Anticoagulants (NOACs) such as Xa inhibitors (rivaroxaban & apixaban) and direct thrombin inhibitors (dabigatran) for VTE management and stroke prevention . Heparin- for VTE prophylaxis, therapeutic use or bridging therapy . If the patient takes anticoagulants: the dose, INR (for warfarin), any problems with maintaining the therapeutic range, medication compliance o Past medical history for non-drug related causes: . Coagulation disorders . Platelet disorders

Summarised by Dr Xinyi (Cynthia) Yang, Intern, Royal Prince Alfred Hospital. April 2016

. Ask especially about congenital diseases (haemophilia, Von Willebrand disease) . Liver and renal diseases can both cause bleeding and affect the clearance of anticoagulant drugs o Family history of bleeding diathesis

 Examination: o Signs of hypovolaemia +/- shock o Focused examination for other sites of bleeding: mucous membrane, skin, chest, abdomen and flanks. Bleeding around the IVC and IDC to suggest coagulopathy o Signs of bleed secondary to platelet dysfunction: muco-cutaneous bleed, petechiae and menorrhagia o Signs of bleed secondary to coagulopathy: large & palpable ecchymosis (muscle haematoma) and haemarthrosis o Palmer/conjunctiva pallor to suggest the extent of anaemia from blood loss and comorbidities

3. Investigations for bleeding diathesis  FBC- drop in Hb lags after blood loss in hyper-acute setting  UEC & CMP: volume status, renal function  LFT- liver function  Coagulation screen (PT, INR, APTT): supra-therapeutically anticoagulated  Fibrinogen and D-dimer: Disseminated Intravascular Coagulopathy (DIC)  Group and hold: prepare for potential transfusion

4. Management of bleeding diathesis, including interpretation of coagulation studies  Before the blood results come back o Call the medical registrar to note the vitals, details of bleed, medications- especially anticoagulants/anti-platelets and what investigation you have ordered o Call the blood bank for 2 units of RBC to be crossed matched in a large bleed. IV fluid in large amount can replace volume but not red cells or coagulants. IV fluids can exert a dilutional effect on and worsen bleeding o Tamponade the wound o Keep the patient warm as hypothermia exacerbates coagulopathy  If the patient is on heparin o Unfractionated heparin prolongs APTT o LMWH will not reliability elevate the APTT, and they are monitored using anti-Xa levels, which is not routinely measured. LMWH is excreted renally and needs dose adjustment in renal failure o Both can be reversed with protamine sulfate  If the patient is on warfarin o INR and PT will be raised o Warfarin can be reversed with vitamin K, fresh frozen plasma and prothrombinex. The exact combination depends on clinical scenario- the severity, site of bleed, INR and local warfarin reversal protocol  If the patient is on a NOAC o Dabigatran: APTT raised more than PT; thrombin time is more sensitive o Rivaroxaban: PT raised more than APTT o Apixaban: neither is particularly sensitive, requires a modified anti-factor Xa level o Potential reversal agents include FFP, prothrombinex, haemodialysis o Overall coagulation assays should not be used to guide drug dosing and reversal of NOACs and the haematology team should be consulted o New agents are becoming slowly available to reverse NOACs Summarised by Dr Xinyi (Cynthia) Yang, Intern, Royal Prince Alfred Hospital. April 2016

 If the patient is on antiplatelet drugs o They affect platelet function; not coagulation studies or platelet count o There is no reversal agents and no evidence for platelet transfusions  Thrombocytopenia o If the thrombocytopenia is due to failure to produce platelets, for example, bone marrow toxicity from chemotherapy, platelet transfusions can be given o One unit of platelet will raise the patient’s count by approx. 25-40 x 10^9/L. o If the thrombocytopenia is due to immunological destruction of platelets, such ITP, platelet transfusions are unlikely to help

5. What other hospital patients are predisposed to bleeding  Very unwell patients, such as septic patients, can develop disseminated intravascular coagulation (DIC), with widespread thrombosis, which consumes platelets and coagulation factors  On coagulation tests, DIC is associated with raised PT and APTT and reduced fibrinogen  Cryoprecipitate, a blood product derived from plasma containing fibrinogen, can be given

6. Take home messages  Bleeding in hospital is often multifactorial. Always consider problems with platelets and coagulation factors  Medication history is crucial, as anticoagulants are often a contributing factor  Significant bleeding requires resuscitation with early use of blood products instead of just fluid boluses  Coagulation testing and interpretation is becoming increasingly complex with the new oral anticoagulants in the market. Consult the haematology team for advice

References Anticoagulation 1: Warfarin with Dr Ed Abadir Anticoagulation 2: Heparins with Dr Ed Abadir Anticoagulation 3: New Oral Anticoagulants with Dr Ed Abadir

Summarised by Dr Xinyi (Cynthia) Yang, Intern, Royal Prince Alfred Hospital. April 2016