You Made the Call
I have two identical cases , which occurred three days apart . Both cases were in young women who presented with acute DVT and significant local symptoms . Both progressed after starting appropriate rivaroxaban 15 mg orally twice a day .
In retrospect , I suspect that both patients had a partial heterozygote antithrombin deficiency that was acutely exacerbated by their DVT . Consequently , at time of presentation , they likely had
IDELVION ® [ Coagulation Factor IX ( Recombinant ), Albumin Fusion Protein ] Lyophilized Powder for Solution for Intravenous Injection Initial U . S . Approval : 2016
BRIEF SUMMARY OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use IDELVION safely and effectively . See full prescribing information for IDELVION .
----------------------------INDICATIONS AND USAGE--------------------------- IDELVION , Coagulation Factor IX ( Recombinant ), Albumin Fusion Protein ( rIX- FP ), a recombinant human blood coagulation factor , is indicated in children and adults with hemophilia B ( congenital Factor IX deficiency ) for :
• On-demand control and prevention of bleeding episodes
• Perioperative management of bleeding
• Routine prophylaxis to prevent or reduce the frequency of bleeding episodes Limitations of Use : IDELVION is not indicated for immune tolerance induction in patients with Hemophilia B .
------------------------DOSAGE AND ADMINISTRATION------------------------ For intravenous use after reconstitution only . Each vial of IDELVION is labeled with the actual Factor IX potency in international units ( IU ).
• One IU of IDELVION per kg body weight is expected to increase the circulating activity of Factor IX as follows :
° Adolescents and adults : 1 . 3 IU / dL per IU / kg ° Pediatrics (< 12 years ): 1 IU / dL per IU / kg
• Administer intravenously . Do not exceed infusion rate of 10 mL per minute . Control and prevention of bleeding episodes and perioperative management :
• Dosage and duration of treatment with IDELVION depends on the severity of the Factor IX deficiency , the location and extent of bleeding , and the patient ’ s clinical condition , age and recovery of Factor IX .
• Determine the initial dose using the following formula :
• Required Dose ( IU ) = Body Weight ( kg ) x Desired Factor IX rise (% of normal or IU / dL ) x ( reciprocal of recovery ( IU / kg per IU / dL ))
• Adjust dose based on the patient ’ s clinical condition and response .
Routine prophylaxis :
• Patients ≥12 years of age : 25-40 IU / kg body weight every 7 days . ( 2.1 ) Patients who are well-controlled on this regimen may be switched to a 14-day interval at 50-75 IU / kg body weight .
• Patients < 12 years of age : 40-55 IU / kg body weight every 7 days .
a profound antithrombin 3 deficiency , leading to failure of therapy of a direct oral anti-10 A inhibitor .
I intend to start these patients on a direct oral thrombin inhibitor for the first month to bypass this potential therapeutic failure .
Maroun Hayek , MD Delta Cancer Institute
Greenville , MS
Switch back to warfarin while we can test for NOAC resistance .
Balbina Gutierrez Gurrola UMAE Hospital De Especialidades CMN
Puebla , Mexico
There is no data suggesting that switching to another NOAC will be better for the patient .
In those cases , I change to warfarin with an INR of 3.0 to 3.5 . Lovenox 1 mg / kg every
-------------------------DOSAGE FORMS AND STRENGTHS---------------------- IDELVION is available as a lyophilized powder in single-use vials containing nominally 250 , 500 , 1000 or 2000 IU .
-----------------------------CONTRAINDICATIONS ------------------------------- Do not use in patients who have had life-threatening hypersensitivity reactions to IDELVION or its components , including hamster proteins .
--------------------------WARNINGS AND PRECAUTIONS-----------------------
• Hypersensitivity reactions , including anaphylaxis , are possible . Should symptoms occur , discontinue IDELVION and administer appropriate treatment .
• Development of neutralizing antibodies ( inhibitors ) to IDELVION may occur . If expected Factor IX plasma recovery in patient plasma is not attained , or if bleeding is not controlled with an appropriate dose , perform an assay that measures Factor IX inhibitor concentration .
• Thromboembolism ( e . g ., pulmonary embolism , venous thrombosis , and arterial thrombosis ) may occur when using Factor IX-containing products .
• Nephrotic syndrome has been reported following immune tolerance induction with Factor IX-containing products in hemophilia B patients with Factor IX inhibitors and a history of allergic reactions to Factor IX .
• Factor IX activity assay results may vary with the type of activated partial thromboplastin time reagent used .
----------------------------ADVERSE REACTIONS--------------------------------- The most common adverse reaction ( incidence ≥1 %) reported in clinical trials was headache .
To report SUSPECTED ADVERSE REACTIONS , contact CSL Behring Pharmacovigilance Department at 1-866-915-6958 or FDA at 1-800- FDA-1088 or www . fda . gov / medwatch .
----------------------USE IN SPECIFIC POPULATIONS---------------------------
• Pediatric : Higher dose per kilogram body weight or more frequent dosing may be needed .
Based on March 2016 version .
12 hours or 1.5 mg / kg every 24 hours is an alternative if the patient accepts daily injections .
William Caceres , MD Universidad Central del Caribe School of
Medicine San Juan , Puerto Rico
Symptomatic PE shortly after starting treatment for proximal DVT is not common , but neither is it rare ; nor is it usually a cause for alarm . It is usually just part of the natural course of DVT / PE . Therapeutic anticoagulation nearly always prevents further thrombosis , although this doesn ’ t happen instantly (“ it takes time to stop a moving freight train ”).
Three possibilities can account for early diagnosis of PE in patients on treatment for a DVT :
1 . Mechanical break-off of some of the leg thrombus : PE comes from proximal DVT – anticoagulation stops further thrombus growth within a short time , but some of the DVT can still break off and cause symptomatic PE in the few days after starting treatment .
2 . Fragmentation of a PE that was already there when anticoagulation started . Remember that about half of patients with a proximal DVT already have a silent PE – some of these will fragment and then produce symptoms in the few days after starting treatment .
3 . True failure of anticoagulation and development of new or worsening of DVT leading to new PE . This is most likely to occur in patients with very thrombogenic cancers ( such as nonsmall cell lung cancer [ NSCLC ]) or in patients with really active antiphospholipid antibody syndrome ( APLAS ).
What I would do in such a case :
1 . Consider whether the patient has features of a scary malignancy or obvious APLAS . However , I would not do thrombophilia testing or search for occult malignancy . You already know he doesn ’ t have NSCLC .
2 . Provide REASSURANCE , REASSURANCE , REASSURANCE .
3 . Absolutely no inferior vena cava filter !
4 . Switch the patient back to apixaban 10 mg twice daily . Switching to another DOAC or to LMWH or warfarin is not rational in this context .
Bill Geerts , MD Sunnybrook Health Sciences Centre
Toronto , Canada
April 2017