Special circumstances

The presence of an intra-cranial tumour on its own is not a contra-indication to anticoagulation but given the risk of bleeding in patients with intra-cranial tumours, anticoagulation should not be commenced until diagnosis of DVT/PE is confirmed radiologically.

Key points from international guidelines and relevant trials are summarised below:

• Choice of anticoagulation, and patient selection is less clear than for other sites as CNS tumours were excluded from the CARAVAGGIO trial of apixaban, but were included in the HOKUSAI trial of edoxaban (although only 72 patients with gliomas or brain mets were represented in the 1005 patients in the trial (7%))
• Data on the safety of DOACs in patients with intra-cranial tumours is limitedto small retrospective case series, but the majority of these suggest that the risk of intra-tumoral haemorrhage maybe lower with DOACs (~5%) than LMWH  (~10%).
• Haemorrhagic CNS metastasis or recent CNS bleed are contraindications to anticoagulation
• A CNS haemorrhage associated with a biopsy, or a previous CNS haemorrhage predating the diagnosis of thrombosis by a significant period of time (e.g. >3 – 6 months), are not absolute contra-indications to anticoagulation. Careful consideration of the risks of further haemorrhage should be balanced with the risks of a PE. 

Brain metastases (cancers other than melanoma/renal cancer) - Although the evidence base is low quality, the risk of intra-cranial haemorrhage appears to be relatively low for patients with brain metastases from sites other than renal cell cancer or melanoma.   

Brain metastases (melanoma/renal cancer) - melanoma and renal cancer brain metastases carry an approximately 4-fold increase in risk of intra-cranial haemorrhage compared to other tumour types but this risk does not appear to be increased by anticoagulation.   

• In the absence of any other contra-indication, anticoagulation should be considered in patients with brain metastases in patients who develop a VTE. 
• Patients with renal cell carcinoma presenting with brain metastases may be considered for whole brain radiotherapy prior to tyrosine kinase inhibitors (TKI) therapy, or in the event of a VTE diagnosis requiring anti-coagulation.  This should be discussed with the patient’s consultant.  

Patients with glioma are at high risk of both thrombosis (up to 30 % of patients with GBM, and 10% of patients with grade 2 or 3 gliomas) and intracranial haemorrhage (5% - 10%).  There are conflicting data on the extent of the increased risk of intra-tumoral bleed for patients with primary glioma and treatment dose anti-coagulation; but most suggest around twice the risk compared to the background bleed rate. This risk will be greatest in patients with GBM and those with a history or prior intra-tumoral bleed. However, in the majority of cases the risks to life and quality of life of the VTE outweigh these risks of an intra-tumoural bleed.

• Patients with GBM should be considered for anticoagulation for treatment of VTE in the absence of any other contra-indications.
• Due to the competing risks of intra-cranial haemorrhage, anticoagulation decisions should always be discussed with the patient’s oncologist or the on-call consultant oncologist.
• A careful discussion of the risks and benefits of anti-coagulation should take place with the patient and be documented in their clinical notes.
• Patients and/or their families should be warned to seek immediate medical attention if they develop sudden onset symptoms of a bleed as they should have a CT head prior to administering more anti-coagulation
• Although monitoring of FBC for patients on anticoagulation is not routinely indicated, for patients at high risk of intra-cranial haemorrhage (risk of HIT or myelosuppressive SACT), regular FBC monitoring (or nadir bloods for SACT patients) would be appropriate on a case-by-case basis.
• Anticoagulation should be suspended while platelets are below 50.

Duration of anticoagulation in patients with glioma:

• For a VTE within 3 months of surgery, in an ambulatory patient with a normal platelet count anticoagulation can be stopped after 6 months
• For a VTE more than 3 months out from surgery; in a patient with poor mobility; or in a patient with a platelet count <150 or >400, anticoagulation should be continued long term.

Thrombus of the splanchnic veins (portal vein, splenic vein and mesenteric veins) is a common complication of cancers involving the hepato-pancreatico-biliary tract. Evidence for the management of splanchnic vein thrombosis is generally low quality, with guidelines largely relying on data from patients without cancer or expert opinion. Reported outcomes in cancer patients with incidental splanchnic vein thrombosis have been drawn from subset population analyses of larger, mostly retrospective studies. It remains unclear if the risk of recurrent thrombosis is higher or lower than the risk of bleeding in this population. 

Strategies for management should consider: 

• Location of the thrombosis (hepatic vein v portal/splenic/mesenteric veins)  
• Primary tumour (hepatocellular carcinoma (HCC) v other) - tumour thrombus within the portal venous system is commonly observed in HCC and should be managed according to HCC guidelines. 
• Presence of cirrhosis or portal hypertension.  
• Hepatic function. 
• Caution if Child-Pugh C, bilirubin > 2xULN, ALT/AST > 3x ULN, albumin<28. 
• Avoid anticoagulation in the presence of a coagulopathy (PT ratio or APTT ratio >1.5). 

Recommendations

• Hepatic vein thrombosis (Budd-Chiari syndrome): 
  • Anti-coagulate in consultation with hepatology in the absence of contra-indications. 
  • Selected patients with extra-hepatic cancers may be suitable for transjugular intrahepatic portosystemic shunt (TIPSS) and should be discussed with hepatology. 
• Acute portal vein thrombosis (with the absence of cavernous transformation of the portal vein or signs of portal hypertension on CT): 
  • Anti-coagulate in the absence of contra-indications.   
  • Selected patients with extra-hepatic cancers may be suitable for TIPSS and should be discussed with hepatology. 
• Chronic portal vein thrombosis (cavernous transformation of portal vein on CT, or evidence of portal hypertension) 
  • Managed on a case by case basis. If concerns about the risks of anticoagulation (specifically the risk of variceal haemorrhage), management of the portal hypertension should be discussed with gastroenterology, with banding of large varices considered. 
  • There is also a risk of significant thrombocytopenia in patients with splenomegaly.  
• Mesenteric vein thrombosis 
  • Anticoagulate in the absence of contra-indications 
  • High risk of mesenteric ischaemia (potentially as high as 45%) and bowel infarction.
• HCC/cirrhosis
  • Splanchnic vein thrombosis is a poor prognostic marker in HCC, but the benefits of anti-coagulation have not been established.   
  • Patients with advanced cirrhosis may already be coagulopathic, and the presence of portal hypertension and splenomegaly will put them at risk of thrombocytopenia. 
    • Consider discussion with hepatology before commencing anticoagulation.
  • Stronger evidence base for anticoagulation for DVT/PE than splanchnic vein thromboses.
  • Anti-coagulate patients with HCC/cirrhosis and PE/DVT unless a clear contra-indication exists.

The most commonly affected superficial veins are the long (great) and short saphenous veins of the leg. Referral for investigation should not normally be necessary for a short segment of below-knee superficial venous thrombosis unless concomitant DVT is suspected.

Patients referred for suspected DVT should be assessed for DVT; if during this investigation a superficial venous thrombosis is identified, management depends on the risk of progression to DVT. 

• If superficial venous thrombosis is within 3 cm of the saphenofemoral junction (SFJ), there is a high risk of progression to DVT. Therapeutic anticoagulation is required for 3 months. 
• For more distal superficial venous thrombosis which is >5cm in length and symptomatic, anticoagulation for 6 weeks can be considered.   
• Otherwise superficial venous thrombosis is a benign and self-limiting condition and distal thrombosis <5cm in length can be safely treated with topical or oral NSAIDs until pain settles. 

Anticoagulation for superficial venous thrombosis can be with either enoxaparin 1mg/kg for 5 days then 1.5mg/kg OD, or off-label use of Apixaban 5mg bd.

1. Massive pulmonary embolism and systemic thrombolysis: refer to PE pathway (only accessible when connected to intranet)
2. Catheter-directed thrombolysis for phlegmasia caerulea dolens/limb-threatening DVT. Patients should be discussed with the on-call vascular surgeon to access this service. 

Andexanet alfa has been granted interim approval by the SMC for use in patients treated with apixaban or rivaroxaban, who require reversal of anticoagulation due to life-threatening or uncontrolled bleeding.  Patients should be discussed with haematology. 

Please consult LUHD Antithrombotic Guidelines (Adults) (only accessible when connected to intranet) and associated protocols.

Anticoagulation with a DOAC reduces the risk of recurrent VTE compared to LMWH, but recurrent thrombosis is still seen, especially in higher-risk cancers such as pancreatic, brain, lung or ovarian cancers.  A common cause of recurrence is lack of compliance with anticoagulation regimen, and this should be explored in the first instance. For patients receiving LMWH, HIT should be excluded as a potential cause for recurrent thrombosis. The evidence base in this setting is limited, but one practice is to treat with supra-therapeutic doses (120 – 125%) of LMWH. There is no evidence for checking anti-Xa levels in this setting. It is unclear whether supra-therapeutic LMWH doses improve clinical outcomes.

Where HIT is not likely or has been excluded, and thrombocytopenia can be attributed to e.g. myelosuppression from SACT, modified anticoagulation strategies can be used. The evidence base for these strategies is weak and reducing or omitting anticoagulation when platelet counts are <50 x10^9/L is reasonable.  Some centres advocate platelet transfusion to facilitate anticoagulation – but this can be impractical, and again the evidence is weak. The following table is found in the 2024 BSH guidelines on treating cancer-associated VTE and thrombocytopenia. 

If dose reductions are being considered this should generally involve a switch to LMWH. so that e.g. intermediate doses halfway between the calculated treatment dose and standard prophylactic doses can be used.  Further advice can be sought from the haematology team if needed.

Options to consider for patients with cancer-associated VTE and thrombocytopenia. An individualised approach is required in all cases [6].