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: ^6,25,26 

• Choice of anticoagulation, and patient selection remain unclear.
• Data on the safety of DOACs in patients with intra-cranial tumours is limited, but one small retrospective study has suggested a low risk of intracranial haemorrhage in these patients²⁷. 
  • CNS tumours were excluded from the CARAVAGGIO trial of apixaban¹, but were included in the HOKUSAI trial of edoxaban¹². 
• 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, are not absolute contra-indications to anticoagulation. Careful consideration of the risks of further haemorrhage should be balanced with the risks of a pulmonary embolism (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^{28, 29}.   

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 ^{30, 31}.   

• 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 glioblastomas are at high risk of both thrombosis (up to 30% of patients) and intracranial haemorrhage (5%-10%). The risk of recurrent thrombosis in patients with a VTE may exceed the risk of haemorrhage^32-36. While intra-cranial haemorrhage in patients with glioblastoma multiforme (GBM) is associated with a poor prognosis, overall the prognosis for anticoagulated patients with a VTE and GBM diagnosis may be similar to GBM patients without a VTE³⁵.

• 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. 
• Although monitoring of FBC for patients on anticoagulation is not routinely indicated, for patients at high risk of intra-cranial haemorrhage (risk of heparin induced thrombocytopenia (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 stopped if platelets fall below 50.

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^{6, 26, 37}. Reported outcomes in cancer patients with incidental splanchnic vein thrombosis have been drawn from subset population analyses of larger, mostly retrospective studies^{38, 39}. 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%⁴⁰) and bowel infarction.
• HCC/cirrhosis
  • Splanchnic vein thrombosis is a poor prognostic marker in HCC⁴¹, 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 considered⁴².   
• 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 dalteparin 200 units/kg, 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.