Table 3.

Existing guideline statements for the management of VTE in patients with thrombocytopenia

GuidanceSetting/topicStatement
ISTH
Scientific and Standardization Committee: Hemostasis and Malignancy, 201826  
CAT, nonsevere thrombocytopenia “Recommend . . . full therapeutic anticoagulation without platelet transfusion to patients with CAT and a platelet count of ≥50 G/L.” 
 Acute CAT (within 30 days) + high risk of thrombus progressiona “[For] severe thrombocytopenia (<50 G/L) and a higher risk of thrombus progression, we suggest full-dose anticoagulation (LMWH/UFH) with platelet transfusion support to maintain a platelet count of ≥40-50 G/L.” 
 Acute CAT (within 30 days) + lower risk of thrombus progressiona For severe thrombocytopenia (<50 G/L) and a lower risk of thrombus progression:
a) Platelet count 25-50 G/L: suggest reducing the dose of LMWH to 50% of the therapeutic dose or using a prophylactic dose.
b) Platelet count <25 G/L: suggest temporarily discontinuing anticoagulation.
c) Recommend resuming full-dose LMWH when the platelet count >50 G/L. 
 Subacute/chronic CAT (>30 days since the index VTE) a) Platelet count 25-50 G/L: suggest reducing the dose of LMWH to 50% of the therapeutic dose or using a prophylactic dose.
b) Platelet count <25 G/L: suggest temporarily discontinuing anticoagulation.
c) Recommend resuming full-dose LMWH when the platelet count >50 G/L. 
American Society of Hematology 2021 guidelines No specific statement regarding management of CAT in the setting of thrombocytopenia  
International Initiative on Thrombosis and Cancer guidelines 2019 and 202218,32  Cancer-associated VTE (treatment) “In patients with cancer with thrombocytopenia, full doses of anticoagulant can be used for the treatment of established venous thromboembolism if the platelet count is >50 G/L and there is no evidence of bleeding; for patients with a platelet count below 50 G/L, decisions on treatment and dosage should be made on a case-by-case basis with the utmost caution (guidance, in the absence of data and a balance between desirable and undesirable effects depending on the bleeding risk vs venous thromboembolism risk).” 
 Cancer-associated VTE (prophylaxis) “In patients with cancer with mild thrombocytopenia with a platelet count >80 G/L, pharmacological prophylaxis can be used; if the platelet count is below 80 G/L, pharmacological prophylaxis can only be considered on a case-by-case basis and careful monitoring is recommended (guidance, in the absence of data and a balance between desirable and undesirable effects depending on the bleeding risk vs venous thromboembolism risk).” 
ESMO Clinical Practice Guideline 202315  Cancer associated VTE, persistent, severe thrombocytopenia (<50 G/L), high risk of thrombus progressionb “Full-dose anticoagulation may be considered in combination with platelet transfusion support aiming at platelet count >40-50 G/L.” 
 Cancer associated VTE, persistent, severe thrombocytopenia (<50 G/L), low risk of thrombus progressionb “Intermediate- to prophylactic-dose LMWH may be considered with temporary discontinuation of anticoagulation if the platelet count falls below 25 G/L.” 
 Cancer-associated VTE, platelet count >50 G/L “Full therapeutic dose anticoagulation should be considered.” 
 DOAC use “Data on the use of DOACs for the treatment of CAT in the presence of severe thrombocytopaenia are lacking.” 
ASCO 2023 Guidelines17  No specific statement regarding management of CAT in the setting of thrombocytopenia  
EHA Guidelines 2022.53  Thrombocytopenia grade 1-2 (platelet count >50 G/L) “Therapeutic-dose parenteral or oral anticoagulation according to the approved indications after a careful evaluation of bleeding and thrombotic risk in the individual patient”
“Thrombocytopenia . . . which is not stable and acute VTE, LMWH should be preferred over DOACs and VKAs.” 
 Thrombocytopenia grade 3 (platelet count 25-50 G/L) “We recommend against using DOACs and VKAs for VTE.”
“LMWH, at doses either prophylactic or therapeutic reduced by 50%, should be used in patients with acute VTE, after balancing bleeding and thrombosis risk.” 
 Thrombocytopenia grade 3-4 (platelet count <50 G/L) “In case of very-high-thrombotic risk, we suggest continuing anticoagulation and increase platelet counts by platelet transfusion or use of TPO-RA.”
“We recommend resuming the appropriate dose of anticoagulation as soon as platelet count allows.” 
UpToDate—anticoagulation in individuals with thrombocytopenia10  Cancer-associated VTE, platelet count >50 G/L “Full-dose anticoagulation is generally appropriate, as in nonthrombocytopenic populations. . . . Close monitoring of the platelet count is warranted, especially if the nadir of chemotherapy-induced thrombocytopenia has not yet occurred.” 
 Cancer-associated VTE, platelet count <50 G/L platelet count 25-50  G/L:
without strong bleeding risk factorsc:
• higher risk for VTE progression or recurrenced: “full-dose anticoagulation with platelet transfusion support (typically, platelet transfusions to raise the platelet count to ≥50  G/L), especially in the presence of another thromboembolic risk factor.”
• lower/intermediate risk for VTE progression or recurrencee or high risk of bleeding: half-dose anticoagulation is the preferred treatment approach for platelet counts between 25-50  G/L; holding anticoagulation is appropriate for platelet counts <25  G/L. other options include prophylactic-dose anticoagulation or temporarily holding anticoagulation.” 
GuidanceSetting/topicStatement
ISTH
Scientific and Standardization Committee: Hemostasis and Malignancy, 201826  
CAT, nonsevere thrombocytopenia “Recommend . . . full therapeutic anticoagulation without platelet transfusion to patients with CAT and a platelet count of ≥50 G/L.” 
 Acute CAT (within 30 days) + high risk of thrombus progressiona “[For] severe thrombocytopenia (<50 G/L) and a higher risk of thrombus progression, we suggest full-dose anticoagulation (LMWH/UFH) with platelet transfusion support to maintain a platelet count of ≥40-50 G/L.” 
 Acute CAT (within 30 days) + lower risk of thrombus progressiona For severe thrombocytopenia (<50 G/L) and a lower risk of thrombus progression:
a) Platelet count 25-50 G/L: suggest reducing the dose of LMWH to 50% of the therapeutic dose or using a prophylactic dose.
b) Platelet count <25 G/L: suggest temporarily discontinuing anticoagulation.
c) Recommend resuming full-dose LMWH when the platelet count >50 G/L. 
 Subacute/chronic CAT (>30 days since the index VTE) a) Platelet count 25-50 G/L: suggest reducing the dose of LMWH to 50% of the therapeutic dose or using a prophylactic dose.
b) Platelet count <25 G/L: suggest temporarily discontinuing anticoagulation.
c) Recommend resuming full-dose LMWH when the platelet count >50 G/L. 
American Society of Hematology 2021 guidelines No specific statement regarding management of CAT in the setting of thrombocytopenia  
International Initiative on Thrombosis and Cancer guidelines 2019 and 202218,32  Cancer-associated VTE (treatment) “In patients with cancer with thrombocytopenia, full doses of anticoagulant can be used for the treatment of established venous thromboembolism if the platelet count is >50 G/L and there is no evidence of bleeding; for patients with a platelet count below 50 G/L, decisions on treatment and dosage should be made on a case-by-case basis with the utmost caution (guidance, in the absence of data and a balance between desirable and undesirable effects depending on the bleeding risk vs venous thromboembolism risk).” 
 Cancer-associated VTE (prophylaxis) “In patients with cancer with mild thrombocytopenia with a platelet count >80 G/L, pharmacological prophylaxis can be used; if the platelet count is below 80 G/L, pharmacological prophylaxis can only be considered on a case-by-case basis and careful monitoring is recommended (guidance, in the absence of data and a balance between desirable and undesirable effects depending on the bleeding risk vs venous thromboembolism risk).” 
ESMO Clinical Practice Guideline 202315  Cancer associated VTE, persistent, severe thrombocytopenia (<50 G/L), high risk of thrombus progressionb “Full-dose anticoagulation may be considered in combination with platelet transfusion support aiming at platelet count >40-50 G/L.” 
 Cancer associated VTE, persistent, severe thrombocytopenia (<50 G/L), low risk of thrombus progressionb “Intermediate- to prophylactic-dose LMWH may be considered with temporary discontinuation of anticoagulation if the platelet count falls below 25 G/L.” 
 Cancer-associated VTE, platelet count >50 G/L “Full therapeutic dose anticoagulation should be considered.” 
 DOAC use “Data on the use of DOACs for the treatment of CAT in the presence of severe thrombocytopaenia are lacking.” 
ASCO 2023 Guidelines17  No specific statement regarding management of CAT in the setting of thrombocytopenia  
EHA Guidelines 2022.53  Thrombocytopenia grade 1-2 (platelet count >50 G/L) “Therapeutic-dose parenteral or oral anticoagulation according to the approved indications after a careful evaluation of bleeding and thrombotic risk in the individual patient”
“Thrombocytopenia . . . which is not stable and acute VTE, LMWH should be preferred over DOACs and VKAs.” 
 Thrombocytopenia grade 3 (platelet count 25-50 G/L) “We recommend against using DOACs and VKAs for VTE.”
“LMWH, at doses either prophylactic or therapeutic reduced by 50%, should be used in patients with acute VTE, after balancing bleeding and thrombosis risk.” 
 Thrombocytopenia grade 3-4 (platelet count <50 G/L) “In case of very-high-thrombotic risk, we suggest continuing anticoagulation and increase platelet counts by platelet transfusion or use of TPO-RA.”
“We recommend resuming the appropriate dose of anticoagulation as soon as platelet count allows.” 
UpToDate—anticoagulation in individuals with thrombocytopenia10  Cancer-associated VTE, platelet count >50 G/L “Full-dose anticoagulation is generally appropriate, as in nonthrombocytopenic populations. . . . Close monitoring of the platelet count is warranted, especially if the nadir of chemotherapy-induced thrombocytopenia has not yet occurred.” 
 Cancer-associated VTE, platelet count <50 G/L platelet count 25-50  G/L:
without strong bleeding risk factorsc:
• higher risk for VTE progression or recurrenced: “full-dose anticoagulation with platelet transfusion support (typically, platelet transfusions to raise the platelet count to ≥50  G/L), especially in the presence of another thromboembolic risk factor.”
• lower/intermediate risk for VTE progression or recurrencee or high risk of bleeding: half-dose anticoagulation is the preferred treatment approach for platelet counts between 25-50  G/L; holding anticoagulation is appropriate for platelet counts <25  G/L. other options include prophylactic-dose anticoagulation or temporarily holding anticoagulation.” 
a

Listed high-risk features: segmental or more proximal PE, proximal DVT, history of recurrent VTE. Listed lower-risk features: distal DVT, incidental subsegmental PE, CRT.

b

Listed high-risk features: first 30 days from thromboembolic event, segmental or more proximal PE, proximal DVT or a history of recurrent thrombosis. Listed low-risk features: more than 30 days from thromboembolic event, distal DVT, isolated subsegmental PE.

c

Listed bleeding risk factors: age over 75 years, recent severe bleeding, hematopoietic SCT, coagulation or platelet function abnormality, kidney/liver failure, increased risk for falls.

d

Listed factors for higher risk: VTE within 30 days, proximal DVT, segmental or more proximal PE. Listed factors for lower risk: isolated distal DVT, isolated subsegmental PE, central-line–associated DVT, or a subacute presentation (ie, >30 days since the acute VTE).

ASCO, American Society of Clinical Oncology; CAT, cancer-associated thrombosis; EHA, European Hematology Association; ESMO, European Society for Medical Oncology; ISTH, International Society on Thrombosis and Haemostasis; TPO-RA, thrombopoietin receptor agonists; UFH, unfractionated heparin; VKA, vitamin K antagonist.

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