Bleeding disorders and risk

Carboplatin & Paclitaxel (CP)

CP: Carboplatin & Paclitaxel

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Forde et al. 2022 (CheckMate 816)	2017-2019	Phase 3 (C)	1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab	Inferior EFS

Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. This study was conducted in the United States. The reason for the study was that an unanswered question at the time was whether adding an immune checkpoint inhibitor would improve outcomes.

Biomarker eligibility criteria

• CheckMate 816: No sensitizing EGFR or ALK mutations

Chemotherapy

• Carboplatin (Paraplatin) AUC 5 or 6 IV once on day 1
• Paclitaxel (Taxol) 175 or 200 mg/m² IV once on day 1

21-day cycle for 3 cycles

Subsequent treatment

• Complete resection

References

1. CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article contains dosing details in manuscript PubMed NCT02998528

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Incomplete information; this section will be expanded, clarified, and with references added in the future.

Initial evaluation

• Bleeding history (acquired or inherited disorder?)
  • Spontaneous or provoked by surgery, tooth extraction, etc.
  • Tolerance of prior surgery
  • Menses
  • Mucocutaneous bleeding, petechiae, oozing at line sites
  • Bruising, hemarthrosis
  • Family history--known hemophilia A, hemophilia B, von Willebrand disease (VWD), platelet function disorder
  • Need for transfusion or product
• History of trauma, surgery
• PT/INR
• PTT
• Platelet count
• +/- fibrinogen (DIC), D-dimer, fibrin/fibrinogen degradation products (FDP)
• Kidney disease (uremia)
• Medications: anticoagulants, antiplatelet medications such as aspirin and Clopidogrel (Plavix), NSAIDS, antidepressants which cause decrease in platelet function

Bleeding Score

This is a quantitative assessment of bleeding risk based on history, and can predict the likelihood of VWD Type I.

• ASH Pocket Guides App contains several calculators including the bleeding score calculator

1. Tosetto A, Rodeghiero F, Castaman G, Goodeve A, Federici AB, Batlle J, Meyer D, Fressinaud E, Mazurier C, Goudemand J, Eikenboom J, Schneppenheim R, Budde U, Ingerslev J, Vorlova Z, Habart D, Holmberg L, Lethagen S, Pasi J, Hill F, Peake I. A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1 VWD). J Thromb Haemost. 2006 Apr;4(4):766-73. link to original article PubMed

Abnormal PT/INR or PTT

• 1:1 mixing study (50/50 mixing study, circulating anticoagulant)
• Liver disease
• Elevated PT only
  • Vitamin K deficiency
    • Warfarin
    • Dietary habits
    • Antibiotic use
    • Malnutrition
    • Increased gut motility
  • Deficiency or inhibitor of factor VII
  • Lupus anticoagulant (rarely)
• Elevated PTT only
  • Heparin
  • Deficiencies of factor VIII, factor IX, factor XI, factor XII, or inhibitors
  • von Willebrand disease
  • Lupus anticoagulant
• Elevated PT & PTT
  • Deficiences of prothrombin (factor II), factor V, factor X, fibrinogen
  • DIC