Coagulation, Haemostasis and interpretation of Coagulation tests

Learning Outcomes Indicate the normal ranges for routine clotting screen and explain what each measurement means Recognise how to detect abnormal results and interpret possible causes Explain what further tests should be performed to help diagnose the cause of abnormal results Explain the use of TEG / RoTEM in monitoring haemostasis Review case studies of normal and abnormal and discuss results and outcomes with group

Haemostasis The vascular phase The platelet phase The coagulation phase

Major components of haemostasis https://www.thrombocyte.com/hemostasis-definition/

Clotting cascade

Simplified clotting cascade APTT measures XII, XI, IX, VIII, X, V, II, I Intrinsic pathway XII, XI, IX, VIII Common pathway X, V, II, I Extrinsic pathway VII Prothrombin Time measures VII, X, V, II, I Fibrin clot

How can we assess haemostasis? Clinical history and examination (e.g. haemostatic challenges) Laboratory tests Coagulation tests Viscoelastic haemostatic testing E.g. TEG/RoTEM

Laboratory: Clotting screening tests Coagulation screen

What do coagulation tests measure? APTT measures XII, XI, IX, VIII, X, V, II, I Intrinsic pathway XII, XI, IX, VIII Common pathway X, V, II, I Extrinsic pathway VII Prothrombin Time measures VII, X, V, II, I Fibrin clot

Prothrombin Time (13-15s) Measures extrinsic pathway Causes of prolonged PT include: Sepsis Warfarin therapy Vitamin K deficiency Liver disease DOACs Practical-haemostasis.com

Activated Partial Thromboplastin Time (APTT) (27-35s) Measures intrinsic pathway Causes of prolonged APTT: Sepsis DOACs Lupus Anticoagulant Heparins Single factor deficiencies Other With prolonged PT: Warfarin/Liver disease/dic

Thrombin Time (13-15s) Prolonged with: Unfractionated Heparin Fibrinogen deficiencies (acquired / congenital) Can have false reading with paraprotein Very prolonged with Dabigatran

Fibrinogen (1.5-4.0 g/l) Reduced in: DIC Massive haemorrhage Liver disease Post-thrombolysis Also reduced in congenital fibrinogen problems NB: usually raised in pregnancy

Reference ranges Physiology and coagulation factors alter with age Premature, newborn, young infants, children, adults different Local reference ranges for the hospital you work at Age range Developed for reagents and coagulation machine

What to do next? Investigations Repeat the sample (if time) If isolated PT check Factor VII level If APTT involved mixing studies Phone a friend the haematology team will help interpret results https://www.youtube.com/watch?v=pwnncir_nla

Management after that Deficiency Factor deficiency needs replacement Except factor XII/Contact factor deficiency If secondary to warfarin/doacs need reversal agents Inhibitors Lupus anticoagulant Other inhibitors rare but serious

Case 1 73yr old man for hip replacement, lives alone. Pre-op clinic bloods: PT 25 (11.5 13) APTT 33.2 (33 36)

What else would you like to know?

A Bleeding History In general: Ever had any haemostatic challenges eg surgery/dental extraction? Epistaxis/gum bleeding? Bruising/easy bleeding? Joint bleed / haematoma? (rare) Menorrhagia (not in this case!) Alcohol Drugs Family history

Causes of an isolated raised PT Warfarin Vitamin K deficiency Liver disease (acute) FVII deficiency (rare)

Case 2 16 year old boy in RTA, bike vs car. Not wearing helmet! GCS 10/15. CT confirms large subdural haematoma. Mum informs you on arrival that patient is on warfarin for Aortic valve replacement (metallic)

What are we going to do?

Warfarin Vitamin K antagonist. Reduces levels of factors II, VII, IX, and X. Long half life & takes a while to get to correct level Reversible with Vit K or PCC Monitored by INR (derived from the PT)

PCC (prothrombin complex concentrate) Fractionated blood component containing vitamin K dependent factors (II, VII, IX and X). Octaplex or Beriplex Given in conjunction with Vitamin K Works rapidly Is blood component, usually managed by blood bank Why do we need to give Vitamin K with PCC?

Warfarin reversal Check your local protocol!! For example only:

FFP is no longer used to reverse warfarin unless you do not have rapid access to PCC

WHAT DO WE DO WHEN HE S STABILISED?

Other anticoagulants: Direct Oral Anti-coagulants Dabigatran is a direct thrombin inhibitor Rivaroxaban/Apixaban/Edoxaban are direct factor Xa inhibitors. Licensed for VTE prophylaxis after hip/knee surgery, treatment of AF, treatment of VTE, prophylaxis after ACS, and more to come Tablets, work quickly, relatively short half life. Don't routinely need monitoring No antidote until recently Relatively expensive

DOAC Reversal As with warfarin, every Trust should have its own protocol for DOAC reversal in emergencies There is a specific reversal agent for Dabigatran idarucizumab (Praxbind) There are agents in the pipeline to reverse Xa inhibitors (none licensed yet) Discuss with Haematology

Low Molecular Weight Heparin (LMWH) i.e Clexane (enoxaparin) Fragmin (Dalteparin) Activates antithrombin Inhibition Thrombin (esp hep) Inhibition FXa Subcutaneous Short Half life Used for prophylaxis of VTE in hospital and treatment of VTE in acute setting Doesn t require monitoring usually Quick acting Partly reversible Renal excretion

Major haemorrhage Laboratory tests vs Near Patient Testing Viscoelastic haemostatic assays: +ves Bedside, rapid results Whole blood (can give indication about platelet function) Davenport et al

Near Patient Testing NICE Diagnostic Guideline 13 2014 www.nice.org ROTEM and TEG recommended to help monitor blood clotting during and after cardiac surgery by healthcare professionals with appropriate training Use as part of research studies in the emergency control of bleeding in trauma and obstetrics Guidance from British Society of Haematology published on use of VHA in 2018 https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.15524

Major Haemorrhage - an example algorithm Trigger major haemorrhage alert Take baseline blood samples Tranexamic Acid TEAM LEADER - Oversees management Co-ordinator liaises with transfusion laboratory Request pre agreed ratio of blood components e.g : 4 units RBC & 4 units FFP IF BLEEDING CONTINUES If lab tests not available FFP and RBC in a ratio of 1:1 Consider Cryoprecipitate (2 pools) If lab tests available Give FFP 15ml/kg if PT/APTT ratio >1.5x normal Cryo 2pools if Fibrinogen <1.5g/l Platelets 1 unit if count <50x10 9 /l Continue monitoring with administration of blood components till bleeding stops

Case 3 35yr old lady Just given birth to baby boy, develops massive post partum haemorrhage After one hour, bleeding improves with local measures. However, bleeding then gets worse with oozing from venepuncture sites and epistaxis

Disseminated intravascular coagulopathy (DIC) Dysregulated fibrinolysis leading to widespread clotting ( using up the clotting factors), and resultant bleeding Patient usually very ill, with bleeding/bruising Prolonged PT/APTT Raised d-dimers Low platelets and fibrinogen.

Management of DIC ABC Treat underlying cause (vital) Blood product support usually only if bleeding (eg in this case) Ask Haematology for help Platelets, FFP, Cryo and Red Cells may all be appropriate