In a nutshell: Abnormal Coagulation Tests and Blood Transfusion

Ng Heng Joo Department of Haematology Singapore General Hospital The typical case

54 year old man • Scheduled for elective hernia surgery

‘…Sir, the anaesthetist has cancelled this case … his bloods are abnormal…may bleed’ How does a patient stop bleeding during surgery (haemostasis)? 1. Vascular smooth muscle contraction 2. Platelet adhesion and aggregation 3. The coagulation system 4. The surgeon The Haemostasis Screen

• Coagulation screen – Prothrombin time (PT) – Activated partial thromboplastin time (aPTT) • Platelet count The Prothrombin Time (PT)

Tissue factor

Calcium Citrate anticoagulated plasma Activated Partial Thromboplastin Time

Surface activating agent e.g kaolin

Phospholipid Citrate anticoagulated plasma Prolongs PTT PT and PTT made easy

HMWK Factor XII PK Factor XI Prolongs PT Intrinsic TF Factor VII Pathway Factor IX Extrinsic Factor VIII Pathway Factor X

Factor V Prolongs PT Common and PTT Pathway Factor II

Factor I PT and PTT made easy PTT HMWK Factor XII PK PT Factor XI Intrinsic Factor VII TF Pathway Factor IX Extrinsic Factor VIII Pathway Factor X

Factor V Common Pathway Factor II

Factor I Possible patterns of the abnormal PT/aPTT

Prolonged PT Normal PT Prolonged PT and aPTT Normal aPTT Prolonged aPTT

Factor VII deficiency Factor VIII, IX, XI or XII deficiency Factor I, II, V or X deficiency or inhibitors or inhibitors or inhibitors Lupus anticoagulant Multiple clotting factor deficiencies The 50:50 Mixing Study

Factor concentrations of 30% or more should give a normal PT/PTT result

One Volume Patient’s Plasma One volume Worse case Normal Plasma scenario All clotting factors Clotting factor at at 100% 0%

Total = 50% In clotting factor deficiencies, the PT or PTT should normalise If PT/aPTT remains prolonged, suspect inhibitors When is the surgeon likely to encounter an abnormal coagulation screen? • Pre-admission or pre-operative screening investigation • As part of investigation for intra or post-op bleeding that is beyond expected norms If I were a surgeon, what does an abnormal coagulation profile mean to me…. • Can I operate? • I need to operate – how can I operate? • I have operated – how will it affect my operation? • My patient is bleeding and it is making me look bad – do I need to and how do I correct it? Is it really necessary to do a pre- operative coagulation screen for all patients? Pre-operative coagulation screening .… what you don’t know cannot hurt you!

Chee YL et al. BJH 2008 The pre-operative coagulation screen

• Indiscriminate coagulation screening prior to surgery or other invasive procedures to predict postoperative bleeding in unselected patients is not recommended. (Grade B, Level III).

• A bleeding history including detail of family history, previous excessive post-traumatic or postsurgical bleeding and use of anti- thrombotic drugs should be taken in all patients preoperatively and prior to invasive procedures. (Grade C, Level IV).

• If the bleeding history is negative, no further coagulation testing is indicated. (Grade C, Level IV).

• If the bleeding history is positive or there is a clear clinical indication (e.g. liver disease), a comprehensive assessment, guided by the clinical features is required. (Grade C, Level IV).

Chee YL et al. BJH 2008 Positive predictive value of abnormal coagulation test for post-op bleeding

Poor (inconsistent) predictive value

Chee YL et al. BJH 2008 The lowdown on PT and aPTT

• In-vitro assays – do not necessarily reflect in- vivo haemostatic response • Best use as diagnostic tests to confirm the presence of a bleeding disorder – not as screening test to detect a bleeding disorder • Normal range excludes 2.5% of healthy people whose results may be above normal The PT and/or aPTT is abnormal Can I ignore an abnormal PT/aPTT?

• No personal or family history of bleeding • Marginal prolongation of 1-2 seconds beyond the normal range Before I call a colleague, what I should probably find out first? • Known congenital bleeding disorder – Haemophilia A and B – Von Willebrand • Known acquired bleeding disorder – Acquired factor inhibitors e.g against factor 8 – Drugs – e.g. anticoagulants – Liver disease – Sepsis/acute DIC • A bleeding history When do I need to give something before surgery? • Most congenital factor deficiencies – Exceptions: factor XII deficiencies, mild factor VII with known bleeding phenotype • Severe sepsis +/- DIC The case of the patient with liver disease • Prolongation of PT and aPTT common in liver disease • Isolated prolonged PT seen in early liver disease due to fall in factor VII • PT and PTT are poor predictors of bleeding • Routine correction of coagulopathy is not required for non-bleeding patients

The patient on anticoagulant

General principals • Wait if possible – allow anticoagulant effect to wear off • If you cannot wait – Warfarin: IV vitamin K AND 4 factor prothrombin complex (4F-PCC) or FFP – Heparin/low molecular weight heparin – protamine sulphate – Non-vitamin K oral antagonist – 4F-PCC The patient with acquired coagulation factor inhibitors • PLEASE…. TRY…… NOT TO OPERATE • If you do, be prepared to file for bankruptcy for patient, doctor and hospital • Use recombinant activated factor VII or FEIBA till such time when bleeding stops The case of the lupus anticoagulant positive patient • aPTT prolonged, PT normal, lupus anticoagulant demonstrated • Patient is however prothrombotic • No correction of aPTT before surgery • Consider VTE prophylaxis after surgery What do I give to correct coagulopathy? • Known single factor congenital deficiency – Haemophilia A: factor VIII concentrates – Haemophilia B: factor IX concentrates – Von Willibrand disease: intermediate purity factor VIII with high vWF – Factor VII deficiency: recombinant activated factor VIIa – Others: fresh frozen plasma Factor inhibitors

• Recombinant activated factor VII (Novo Seven) • FEIBA Are there numerical guides on when I should correct an abnormal coagulation profile before surgery? • INR >1.2 for surgery in critical areas • INR > 1.5 for major surgery in non-critical areas • PT and aPTT > more than 1.5x the mid-point of the normal range If I give fresh frozen plasma, how much should be given? • 10-20 mls per/kg • For the average size individual, at least 750 mls (approx. 3 packs) The platelet count – what is a ‘safe” number for surgery • 50 x 109/L for major surgery in non-critical areas • 100 x 109/L of surgery in critical areas e.g intracranial, spinal, ocular surgery Packed red cell transfusion

General principles • Hb >10 gm/dl – very little justification for transfusion • Hb<7 gm/dl – beneficial especially when symptomatic or if there is ongoing blood loss • Hb 7-10gm/dl – individualized. Assess symptoms and signs, co-morbidities, evidence of ongoing blood loss or potential for blood loss

Singapore Med J 2011; 52(3) : 211 Thank you