Week 3 - Issues in thrombosis - Thrombophilia/Thromboprophylaxis - & MAssive haemorrhage protocol (PPH/Trauma/Variceal)

Question 1

Scenario 1 A 17-year-old girl presents to Accident and Emergency with a 24 hour history of a swollen right leg. She has had no previous significant illnesses, smokes 15 cigarettes per day and her only medication is the oral contraceptive pill. Her mother has had three thromboses (“legs and chest”) and her grandmother died aged 46 of unknown cause.  What is your working diagnosis to explain the swollen leg? Explain risk factors she has?

Answer 1

Swollen right leg - could be cellulitis or DVT Arterial thrombosis - smoking - only risk factor stated Venous thrombosis - On the oral contraceptive pill - increases hypercoagualbility and family history of DVT/PE, female is also a risk factor Likely she has had a deep vein thrombosis

Question 2

What is the mechanism for venous thrombosis?

Answer 2

* It is all related to virchows triad * Stasis, endothelial damage and hypercoagulability Veins are low pressure vessels relying upon the leg muscles to pump blood back and valves to prevent backflow of blood, if the blood remains in the legs ie long periods of immobility (stasis) it can pool and form a fibrin clot Hypercoagulable blood means blood will clot easier Endothelial damage releases tissue factor which starts the extrinsic clotting pathway

Question 3

When is hereditary thrombophilia screening considered? What is thombophilia?

Answer 3

Considered if venous thrombosis <45 Recurrent venous thrombosis Unusual site of venous thrombosis ie portal vein thrombosis Family history of venous thrombosis Family history of thrombophilia Thrombophilia is an inherited or acquired disorder resulting in an incresed coagulability

Question 4

What are the 5 main types of hereditary thrombophilias that would be screened for in a patient who presented as this 17 year old female did? (she had both a venous thrombosis <45 and a family history of venous thrombosis)

Answer 4

Factor V leidin - most common - point mutation in factor V makes it resistant to the action of activated protien C resulting in no natural anticoagulant effect Prothrombin gene mutation - prothrombin G20210A mutation - guanine changes to adenine at the 20210 position on the DNA of prothrombin - results in excessive prothrombin in the blood Anti-thrombin deficiency Protein C and Protein S deficiency

Question 5

Scenario 2 A 68-year-old lady with disseminated breast cancer has fallen and suffered a pathological fracture of her right femur which requires surgery to pin the femur and stabilise the fracture. She is 15 stone in weight and will expect to spend a week in bed post-operatively.  List the non-inherited risk factors for venous thrombosis.

Answer 5

Non-inherited risk factors Malignancy - release of tissue factor - hypercoagulable Trauma - damage to endothelium Obesity - immobility and increases procoagulants Bed rest - immobility - stasis of blood Age - valves may have degenerated slightly leading to stasis

Question 6

 What measures could be taken to reduce the thrombotic risk in this case. ie post operative Discuss the mechanism of action for each method discussed.

Answer 6

Could give her a LMWH - this potentiates the action of anti-thrombin III to bind to and inactivate factor Xa * Could give a new oral anti coagulant - either factor Xa inhibitor eg rivoroxaban or apixaban or * Factor IIa inhibitor - eg dabigatran * TED Stockings - compress the calves to resume muscular pump of blood back to heart * Intermittent pneumatic compression - if there is a long surgery -artificially mimics muscle movement to pump blood back Also ensure early mobilisation post-operation

Question 7

Now lets talk about massive haemorrhage and its treatment protocol Massive haemorrhage can either be defined by volume and rate of blood loss Or by the clinical situation How is massive haemorrhage defined by the volume and rate? What is minor and major loss for PPH (obstetrics)?

Answer 7

One blood volume loss in 24 hours 50% blood loss in 3hours 150mls/min of blood loss in the patient In post partum haemorrhage - a minor blood loss is greater than 500 mls and a major blood loss is greater than 1000mls Both fall under the massive haemorrhage protocol

Question 8

One blood volume loss in 24 hours 50% blood volume loss in 3hours 150mls lost per minute Obestetrics - 500-1000mls PPH = minor, >1000mls PPH = major These are massive haemorrhages defined by volume and rate of blood loss How can massive hemorrhage be defined clinically?

Answer 8

Bleeding which leads to a heart rate greater than 100bpm and systolic BP <90mmHg Bleeding which ha already prompted the use of Group O RhD negative blood

Question 9

What are the 4 causes of post partum haemorrhage? How does the main cause work? What is the normal blood loss in a vaginal delivery? What can be givered in the third stage of loabour as prophylaxis to post partum haemorrhage?

Answer 9

Tone - Uterine atony - normally uterus contracts compressing the blood vessels and reducing blood flow increasing coagulation. In uterine atony the uterus doesn’t contract and therefore the vessels continue to bleed Trauma Tissue - Retained placental tissue Thrombin - Coagulopathy Normal blood loss in vaginal delivery - 500ml Can give oxytocin in 3rd stagee of labour as PPH prophylaxis

Question 10

What is the treatmnt of post partum haemorrhage? (1st line) Talking about the treatment to stop the bleeding Will discuss replacing the lost components of blood separately

Answer 10

Bimanual uterine massage for uterine atony and give 5units oxytocin

Question 11

If oxytocin, doesnt work to stop the bleeding, what can be given?

Answer 11

Give ergometrine - if this doesnt work Can try giving prostoglandin analogues such as carboprost or Tranexamic acid - antifibrinolytic - will prevent the breakdown of clots

Question 12

What surgical procedures may be carried out to treat PPH?

Answer 12

May have to carry out a B-lynch brace uterine suture to compress the uterus and prevent further bleeding In PPH, most woman respond to the utero-tonic agents

Question 13

Blood component support is basically there to support the patient whilst yous top the bleeding What is a massive haemorrhage protocol?

Answer 13

This is a protocol facilitating the prompt transfusion of appropriate blood and blood components and allows a standardised approach to the initial management of massive haemorrhage

Question 14

Activation of the massive haemorrhage protocol allows emergency issue of blood components for bleeding patients without the authorisation of a haematologist if someone comes in and you suspect a massive haemorrhage, what should be the first step?

Answer 14

Call ninewells and state massive haemorrhage and the ward Call the blood bank and state massive haemorrhage as well

Question 15

Ideally fully crossmatched bloods would be issued for any red cell transfusion but in massive haemorrhage there may not be time to wait around What are the three optionss?

Answer 15

* Can use the emergency O RhD negative, Kell negative blood that is on the wards * Can wait 20 minutes to use group specific red cells where the ABO & RhD status have been confirmed but the irregular antibody status has not been * Can wait one hour to have ABO,RhD and antibody status confirmed O neg cells (immediate), group specific cells (20 minutes) or fully crossmatched cells (within one hour)

Question 16

It is important to take blood from the patient to send for checking Looking for FBC, coagulation screen, Fibrinogen, crossmatch, U&Es and calcium levels What will the blood ban issue now they have been called?

Answer 16

The blood bank will issue 4 units red cells, 4 units of FFP and 1 unit of platelets

Question 17

If trauma causing the massive haemorrhage happened in the last 3 hours, what is useful to give? What is the rate at which the Redcells / FFP / Platelets are transfused in?

Answer 17

If trauma occured within the last 3 hours - give 1g tranexamic acid to stop the bleeding Transfused 2units Red cells to 1unit FFP (in trauma it is transfused in a 1:1 ratio) and transfer one unit of platelets

Question 18

When blood results become available it is important to take bloods every half an hour to check for the levels of Hb, APTT and PT, Platelets, and Fibrinogen What should we be aiming to maintain these levels at?

Answer 18

Hb >80g/L APTT and PT 50x10^9 / L Fibrinogen >1,5g/L and greater than 2g/L in obstetric haemorrhagies

Question 19

Ongoing transfusion required if the bleeding continues What are the values we aim to maintain again? What is given if fibrinogen is below what normally and below what in obstetric emergencies?

Answer 19

Hb>80g/l APTT and PT 50x10^9/L Fibrinogen >1.5g/l and greater than 2g/L in obstetric haemorrhages If the fibrinogen levels are below than 1g/l in haemorrhage then give cryoprecipitate, if it is below than 2g/l in obstetric haemorrhages then give cryoprecpitate

Question 20

Important to let blood bank know when bleeding has stopped What should be considered once the bleeding has stopped and why? Why is the fibrinogen requirements higher during pregnancy than when not?

Answer 20

Once the bleeding has stopped, consider giving thromboprophylaxis as there has been a huge activation of coagulation factors here and therefore patient may be at severe risk of DVT/PE Fibrinogen measurements are expected to be higher during pregnancies as it is one of the coag factors that increase during pregnancy

Question 21

If measuring fibrinogen levels in a pregnant women with fibrinogen levels and they are low - this means they are actively very low as fibrinogen should be high during pregnancy – therefore important to give cryoprecipitate Rememeber blood ban issues 4units Red cell/ 4 unit FFP / 1 unit Platelets * What is the ratio that they are given in? * When is cryoprecipitate given? * What lvls of blood that are monitored are aimed for?

Answer 21

Give 2units red cells to 1 unit FFP unless trauma where it is 1:1 Cryoprecipitate is given if bloods come back and fibrinogen is * Hb>80g/L * Platelets >50x10^9/L * APTT and PT 1.5g/l and greater than 2g/l in obstetric haemorrhages

Question 22

What is given in the treatment of variceal bleeding? 1st and 2nd line

Answer 22

Terlipressin - a vasoactive drug is given to try and reduce the bleeding and Endoscopic band ligation is given to stop the bleed If these do not work TIPSS can be attempted - trans-jugular intrahepatic portal systemic shunt

Question 23

If unable to perform endoscopic ligation or TIPSS, can perform balloon tamponade which can be effective in arresting haemorrhage as a temporary measure (for up to 24 hours) until endoscopic variceal ligation and/or TIPS is carried out. What can be given as prophylaxis to oesophageal variceal bleeds in patients with liver cirrhosis?

Answer 23

can give propranolol - bblocker