Quick Tip; The most common causes for a prolonged PT are vitamin K deficiency and sepsis
A prolonged prothrombin time is incredibly common in inpatients as the inpatient population are commonly admitted with infection/sepsis and can be nutritionally deplete, both of which cause prolongation of the PT. Infection and sepsis processes consume clotting factors, commonly affecting both the PT and APTT (although PT usually more so as factor VII has one of the shortest half lives of all clotting factors), and nutritional deficiency or malabsorption of vitamin K inhibits production of vitamin K-dependent clotting factors.
If on repeat the PT remains prolonged and is felt to be due to factor consumption or nutritional deficiency;
If urgent correction is needed when prolongation is due to warfarin;
If urgent correction is needed when prolongation is not due to warfarin;
Links: Practical Haemostasis
Quick tip; Prolonged APTT is more likely to indicate underlying factor deficiency than a prolonged PT
Prolonged APTT is a more likely to indicate an underlying clotting disorder than a prolonged PT, but certain test anomalies and other clinical conditions need excluding before testing for these conditions is undertaken.
Note 'Short APTT'
This result is seen most often due to acute inflammation increasing factor VIII levels or pre-activation of the clotting cascade during the sampling process (see link below).
This is somewhat of a misnomer as a lupus anticoagulant confers a higher thrombosis risk than one of bleeding, but due to the way it prolongs the APTT, it has gained the name lupus anticoagulant. These can often be transient (e.g post viral infection) therefore must be repeated at 3 months to see if they are still present. If there is a thrombosis history, thrombophilia testing is indicated only when considering stopping anticoagulation as only at that point will it change management. Also some clotting tests are affected by the presence of acute thrombosis and by anticoagulants e.g DOACS.
Quick tip; Low Molecular Weight Heparin (LMWH) monitoring should be performed if suspicious of supratherapeutic or subtherapeutic treatment.
LMWH can be monitored with Anti-Xa levels if suspicion of inadequate treatment/overdosing. This occurs most commonly in these patient groups;
To check adequate dosing;
If concerns about accumulation of LMWH due to renal impairment;
Split dosing of LMWH can be used if;
Quick tip; DIC will not resolve without management of the trigger
Disseminated intravascular coagulation is a process of extreme hypercoagulability following a trigger such as sepsis or bleeding. It results in microthrombosis leading to organ injury, and can be followed by a significant bleeding risk from consumption of clotting factors and platelets (although only up to 12% in published studies (see 'How I treat DIC' article link below)). The condition requires urgent intervention with management of the cause and blood product support as indicated clinically, since DIC increases trauma mortality two- to four-fold, and mortality in obstetric sepsis.
Note it is important to use the Clauss fibrinogen rather than the standard (derived) fibrinogen as the derived test can commonly be falsely elevated
The likelihood of DIC depends on the number of these features being present, measured in context of a potential trigger. See the Blood 'How I treat DIC' article for more on the DIC scoring system and some case examples of DIC
Quick Tip; The 4 T's score for HIT is a validated score to guide management
Heparin induced thrombocytopenia (HIT) is a phenomenon induced by antibodies to platelets which are formed after heparin exposure. This can occur either during the first exposure episode or up to 100 days later, with a quicker onset of thrombocytopenia, once re-exposed. A thorough history is therefore critical to identify any history of exposure to heparin in any form over the previous 100 days.
HIT should be suspected in any patient who develops thrombocytopenia after being being exposed to heparin. Differential diagnosis (in often very unwell patients) include;
If the HIT score is intermediate or high this will usually merit a HIT blood test. Depending on laboratory processes, there is usually a high sensitivity, intermediate specificity screening test, and if positive the sample will be sent for further, more specific testing.
If the score is low, it is unlikely to be HIT but if other diagnoses seem very improbable discuss with haematology.
Links; BSH Guideline
Quick Tip; The greatest risk factor for VTE in travellers is a history of VTE
There is a general increase in venous thromboembolism (VTE) in long-haul travellers (over 4.5 hours) that may be higher in air travel but should be risk-assessed regardless of the mode of travel.
Risk factors and appropriate management are listed below in terms of severity;
Above adapted from NICE CKS (ref below)
If the patient has had a VTE in the last 2 weeks travel is usually not be recommended while anticoagulation is established. After 2 weeks however if the patient has tolerated the anticoagulation well, the patient could be viewed as being low-risk and should be managed as such.
Aspirin is NOT recommended as a method of prophylaxis.
Quick tip; Certain thrombophilia tests cannot be interpreted during an acute episode of VTE, or whilst on certain anticoagulants
Good management of deep vein thrombosis (DVT) is important to minimise local sequelae of DVT such as post-thrombotic syndrome and the risk of pulmonary embolus (PE). Further management should include investigation for a trigger if indicated. DVT and PE exist as part of the spectrum of venous thromboembolism (VTE) and many of the general investigations for them are similar.
Most VTEs are secondary/provoked. Causes include;
When there is no obvious trigger, in the case of DVT, it is classified as 'unprovoked DVT' which merits a basic screen for underlying cancer (note this has changed in the NICE 2020 update) . This should include;
Thrombophilia testing can be considered after a first unprovoked DVT/PE but only at the point of stopping anticoagulation, as thrombophilia screens are not reliable at the time of an acute VTE, and offer no benefit if anticoagulation is to be continued. Inherited thrombophilia is most likely if there is a family history of thrombophilia, or skin necrosis with warfarin (proteins C/S deficiency). These could include;
Links: NICE Venous thromboembolic diseases: diagnosis, management and thrombophilia testing 2020
Quick Tip; Check when the patient last had a dose of their DOAC, as this may show that the DOAC is unlikely to still be in circulation and therefore no longer a risk factor for bleeding.
DOACs are increasingly chosen for VTE treatment and AF stroke prophylaxis for their ease of use, both by clinicians and patients. Bleeding on DOACS however is still an area with a very limited evidence base. A normal coagulation screen does not necessarily mean no DOAC on board, as different laboratories will have different sensitivities to the drugs. This is especially true for apixaban whereby therapeutic levels frequently result in a normal standard coagulation screen.
Does my patient still have a DOAC 'on-board'?
It is critical to find out, if possible, when the last dose of DOAC was taken, as although DOAC levels can be done, it takes time, and interpretation of results sadly does not have a clear cut-off for those at risk of bleeding or not. It is important to therefore consider drug half lives;
Broadly speaking, in the presence of normal renal function, manufacturers advise avoiding low bleeding risk surgical procedures for 24 hours after the last dose, and high bleeding risk procedures for 48 hours after the last dose. This gives an indication of the suspected bleeding risk i.e most or all of the DOAC should be cleared by 24 hours after the last dose, but the manufacturers recommend 48 hours in elective high bleeding risk surgery. Consider this when reviewing a patient with bleeding on a DOAC.
Bleeding on Dabigatran (thrombin inhibitors)
Dabigatran has an antidote-idarucizumab, which is widely available in the UK and works quickly, with an antidote effect for up to 24 hours or more (Pollack et al. NEJM. 2015). Some centres will have protocols so that haematology do not need consulting before use, others require it to be 'released' by a haematologist-check local practice. A thrombin time is useful- this can be added to a standard coagulation screen and if normal, effectively rules out any active dabigatran in circulation (Keeling et al. Br J Haem. 2016).
Bleeding on Apixaban, Rivaroxaban and Edoxaban (Xa inhibitors)
For apixaban and rivaroxaban there is now a licensed reversal agent, andexanet, but this is only approved for a very specific indication (life-threatening/uncontrolled bleeding from the GI tract when there is a plan for procedural (almost always endoscopic) intervention. Data from patients outside this specific indication showed no significant benefit, and in some cases potentially increased harm. Local guidance should be followed if andexanet felt to be appropriate, and cases should be discussed with endoscopists as they will be making decisions regarding endoscopic interventions and thus suitability for the drug.
Andexanet is not licensed for edoxaban reversal.
The following measures are useful general principles for all cases of bleeding on DOACs;
In summary, follow local guidelines but broadly speaking; check for other bleeding risks, perform local haemostatic measures and use tranexamic acid. PCC can be used for severe bleeds and there is weak evidence it may help if no other options are available, but the risk of thrombosis is not minimal. Discuss with haematology if this is being considered. If the case is complex or elements are unclear (e.g when last dose was taken) discuss with haematology for DOAC levels and advice on PCC use.
Pollack et al. 2015 NEJM https://www.ncbi.nlm.nih.gov/pubmed/26095746
Keeling et al. 2016 Br J Haem https://www.ncbi.nlm.nih.gov/pubmed/27714755
Arachchillage et al 2019 Br J Haem https://www.ncbi.nlm.nih.gov/pubmed/30515764
WOMAN trial collaborators. 2017. The Lancet https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446563/
Roberts I et al. 2013. CRASH-2 study. Health Technology Assessment https://www.ncbi.nlm.nih.gov/pubmed/23477634
Andexanet data - Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors NEJM
NICE andexanet technology appraisal 1 Recommendations Andexanet alfa for reversing anticoagulation from apixaban or rivaroxaban Guidance NICE
Northumbria Healthcare NHS Foundation Trust guideline for reversal of DOACs. Many thanks to Dr Charlotte Bomken for her permission to exhibit this guideline. This guideline is listed as an example and is for information only. Follow local guidelines when managing individual patients.
Quick tip; Inferior Vena Cava filters should be avoided unless absolutely needed, as they are often left in situ beyond the recommended period, and are associated with significant patient morbidity if so
Inferior vena cava filters are indicated in patients with deep vein thrombosis (DVT) when anticoagulation is contraindicated. They aim to 'trap' any emboli leaving the DVT and passing to the lungs, which would become a pulmonary embolus (PE). These can be of critical important in patients who have, for example, an ongoing imminent need for surgery, or unstable bleed in a critical area e.g the brain.
The evidence around IVC filters is controversial, but a large systematic review and meta-analysis (Bikdeli et al. 2017) (with 1,986 studies of low to moderate quality) did show a reduction in PE risk with use (OR: 0.50; 95% confidence interval [CI]: 0.33 to 0.75), albeit with an increased DVT incidence (OR: 1.70; 95% CI: 1.17 to 2.48).
The problem with IVC filters is that they are often requested by the team caring for the patient during the acute episode, and inserted by interventional radiology, and it may be that after this episode, neither team has routine follow up with the patient, and the IVC filter is 'forgotten'. 'Forgotten' IVC filters are common, one large retrospective study (Jia et al. 2018) identified 13% of patients who had had the filters inserted were lost to follow up, and a further 4% remained in place due to 'physician oversight'. 2% of patients with IVC filters still in situ had PE, 7.7% had recurrent DVT, 5.4% had vessel wall penetration and almost 10% of patients who had an attempted retrieval, could not have their filter removed.
Prophylactic IVC filters in trauma patients - an NEJM paper from 2019 (Ho K, et al 2019) showed that prophylactic IVC filter placement in patients with severe trauma in whom prophylactic anticoagulation was contraindicated, did not reduce incidence of pulmonary embolism compared to those that had no filter sited. In those who had no anticoagulation of any kind by day 7 after trauma, there were incidences of PE in the control arm, but not the filter arm. This was not statistically significant, but does highlight the importance of starting prophylactic anticoagulation as soon as possible, once haemostasis is stable and considering alternative methods of thrombosis risk reduction such as pneumatic compression where appropriate.
IVC filters have a proven benefit in reducing PE in those who cannot receive anticoagulation in the context of a known DVT. However they also have a proven risk of increased subsequent DVT, no role as a prophylactic measure in major trauma patients, and can be 'forgotten' with significant morbidity for the patient (DVT, occlusion and leg swelling). Therefore, be sure that they are being placed for the right indication, and that there is a plan for removal with a named individual responsible for that. Use prophylactic anticoagulation as soon as possible and consider alternative thrombosis risk reduction strategies as appropriate.
Inferior Vena Cava Filters to Prevent Pulmonary Embolism. Bikdeli et al. Journal of the American College of Cardiology. Volume 70, Issue 13, September 2017. DOI: 10.1016/j.jacc.2017.07.775
Utility of Retrievable Inferior Vena Cava Filters: A Systematic Literature Review and Analysis of the Reasons for Nonretrieval of Filters with Temporary Indications. Jia K, et al. Cardiovasc Intervent Radiol. 2018 May;41(5):675-682. doi: 10.1007/s00270-018-1880-9.
A Multicenter Trial of Vena Cava Filters in Severely Injured Patients. Ho K, et al. N Engl J Med 2019; 381:328-337