SAUDI MOH PROTOCOL FOR VACCINE-INDUCED THROMBOSIS AND THROMBOCYTOPENIA (VITT)
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Saudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
Disclaimer: This is a living guidance that is subject to change as more evidence accumulates. It will be updated regularly and whenever needed.
INTRODUCTION:
• Vaccines are important for managing the COVID-19 pandemic caused by SARS-CoV-2.
• Reports have emerged of some vaccine recipients developing unusual thrombotic events and thrombocytopenia.
• Between Dec 2020 and Mar 2021, European Medical Agency approved 4 vaccines:
o BNT162b2, mRNA encoding spike protein antigen encapsulated in lipid nanoparticle
o mRNA-1273, encoding spike protein antigen encapsulated in lipid nanoparticle.
o ChAdOx1 nCov-19, a recombinant chimpanzee adenoviral vector encoding spike glycoprotein.
o Ad26.COV2.S, a recombinant adenovirus type 26 vector encoding spike glycoprotein.
• First cases of thrombosis with thrombocytopenia reported in Feb/Mar 2021 with ~15-20M doses.
• Because of the rarity of these events and the potential severity of COVID-19, the European Medicines Agency (EMA) concluded that the
overall benefits of the vaccine continue to outweigh the risk.
• The WHO stated that a causal relationship, while plausible, has not been confirmed, and that the very rare incidence should be weighed against the
risk of morbidity from COVID-19.
• Covid-19 vaccine induced thrombosis and thrombocytopenia (VITT) is a very rare complication following vaccine exposure.
• Some experts have suggested that these events could be related to vaccine-induced autoantibodies directed against a PF4 platelet antigen, similar to
those associated with heparin-induced thrombocytopenia (HIT).
• Typical presentation is 4-28 days following administration of vaccine.
• Recipients of any vaccine should be aware of the possible association and seek immediate care for signs and symptoms suggestive of
thrombocytopenia (petechiae around the vaccination site after several days) or thrombotic complications (including shortness of breath, chest pain,
lower extremity edema, persistent abdominal pain, unabating severe headache, focal neurologic symptoms, and seizures).
• Among approximately 34 million vaccine recipients in the United Kingdom and European Economic Area, there were 169 cases of cerebral venous
sinus thrombosis (CVST) and 53 cases of splanchnic vein thrombosis reported through safety surveillance systems however, VTE occurring in other
sites cannot be excluded.
1Saudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
EVALUATION:
• Any patient with unusual symptoms within 28 days of receiving vaccine with symptoms of VITT (persistent and severe headache; focal neurological
symptoms (including blurred vision); shortness of breath; abdominal or chest pain; swelling and redness in a limb; or pallor and coldness in a limb
should be assessed by health care provider and should report to SFDA.
• Patients with severe symptoms should urgently seek medical attention at their nearest emergency department.
DIAGNOSIS:
• ‘Diagnosis of exclusion’ as there is currently no validated confirmatory assay.
• Timing of vaccine (4 – 28 days prior to presentation).
• Unexplained platelet count less than 150x 109/L orSaudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
4. Evidence of thrombosis and D-Dimer 2-4mcg/mL or D-Dimer >4mcg/mL .
CONFIRMED CASE:
1. Onset of symptoms between 4-28 days after vaccination.
2. Platelet countSaudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
Symptoms of VITT
Persistent and severe headache, focal neurological
POSSIBLE CASE symptoms, seizures, blurred vision, shortness of breath,
chest or abdominal pain, swelling and redness in a limb,
pallor and coldness in a limb
Onset between 4-28 days after vaccination
• CBC to confirm thrombocytopenia
Do not proceed to HIT testing Unlikely No Yes • PT,aPTT, D-Dimer, fibrinogen
• Imaging to check for thrombosis
• Platelets >150 × 109/L or 150 × 109/L
base line PROBABLE • Platelets >150 × 109/L
CASE orSaudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
Medication Related Information
Required dose
Medication Contraindication Major Drug Interactions Pregnancy
adjustment
- Anaphylactic or - To Consider therapy modification. - Dosing: Renal - Placental transfer of
Intravenous severe systemic Impairment: Adult human IgG is
Immunoglobulin reaction to human o Vaccines (Live): Immune Globulins may diminish the therapeutic effect of Vaccines IV: Use with caution due dependent upon the
(IVIG) immune globulin (Live). Management: Consult full interaction monograph for dose interval to risk of immune IgG subclass and
recommendations. This interaction does not apply to oral Ty21a typhoid vaccine or globulin-induced renal gestational age,
Dose: 1g/kg/day - IgA-deficient others listed as exceptions. dysfunction; the rate of
for 2 days patients with infusion and - Exogenous immune
antibodies against concentration of solution globulin was shown to
IgA and history of should be minimized. cross the placenta
hypersensitivity to Discontinue if renal similar to endogenous
human immune function deteriorates immune globulin.
globulin treatment during treatment.
IM: There are no dosage
adjustments provided in
the manufacturer's
labeling.
SubQ infusion: There
are no dosage
adjustments provided in
the manufacturer's
labeling; consider lower,
more frequent dosing.
- Dosing: Hepatic
Impairment: Adult
IM, IV, SubQ infusion:
There are no dosage
adjustments provided in
the manufacturer's
labeling.
- Dosing: Obesity: Adult
Some clinicians dose
IGIV on ideal body
weight or an adjusted
ideal body weight in
5Saudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
Medication Related Information
Required dose
Medication Contraindication Major Drug Interactions Pregnancy
adjustment
morbidly obese patients
(Siegel 2010).
Fondaparinux - Active major • Avoid combination - Renal impairment, CrCl Pregnancy
(first line) bleeding o Apixaban: May enhance the anticoagulant effect of Anticoagulants. 30 to 50 mL/min: Use Considerations
o Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. with caution
o Edoxaban: May enhance the anticoagulant effect of Anticoagulants (manufacturer dosing) Based on case
- Body weight less
Dose: o Hemin: May enhance the anticoagulant effect of Anticoagulants. reports, small amounts
than 50 kg in
(2.5 mg/0.5 mL, o Mifepristone: May enhance the adverse/toxic effect of Anticoagulants. - Renal impairment, CrCl of fondaparinux have
patients requiring
5 mg/0.4 mL o Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of 20 to 50 mL/min (VTE been detected in the
prophylaxis for
7.5 mg/0.6 mL Omacetaxine. prophylaxis): 1.5 mg umbilical cord
venous
and o Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of subQ once daily starting following multiple
thromboembolism
10 mg/0.8 mL) Rivaroxaban. 6 hours or more (ideally doses during
injection. o Urokinase: May enhance the anticoagulant effect of Anticoagulants. 8 hours) postoperatively pregnancy
- History of serious o Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. for10 days for total hip (Dempfle2004). Use of
hypersensitivity or knee replacement or fondaparinux in
reaction (eg, • To Consider therapy modification. 28 to 35 days for hip pregnancy should be
angioedema, o Desirudin: Discontinue treatment with other anticoagulants prior to desirudin fracture surgery (study limited to those
anaphylactoid or initiation. If concomitant use cannot be avoided, monitor patients receiving these dosing) women who have
anaphylactic combinations closely for clinical and laboratory evidence of excessive severe allergic
reactions) anticoagulation. - Geriatric: Use with reactions to heparin,
o Estrogen Derivatives: Carefully weigh the prospective benefits of estrogens against caution including heparin-
the potential increased risk of procoagulant effects and thromboembolism. Use is induced
- Severe renal
considered contraindicated under some circumstances. Refer to related guidelines - Hemodiafiltration in thrombocytopenia,
impairment (ie, CrCl
for specific recommendations. patients with heparin- and who cannot
less than 30
o Herbs (Anticoagulant/Antiplatelet Properties): Avoid such combinations when induced receive danaparoid
mL/minute) thrombocytopenia:
possible. If used concomitantly, increase diligence in monitoring for adverse effects (Guyatt 2012).
Thrombocytopenia (eg, bleeding, bruising, altered mental status due to CNS bleeds). Initiate at 0.03 mg/kg
associated with Progestins: Carefully weigh the prospective benefits of progestins against the potential postdialysis body
positive in vitro test increased risk of procoagulant effects and thromboembolism. Use is considered weight, administered via
for antiplatelet contraindicated under some circumstances. Refer to related guidelines for specific the efferent line of the
antibody in the recommendations. dialyzer; titrate in
presence of increments of 0.01
fondaparinux mg/kg postdialysis body
sodium weight based on
postdialysis anti-Xa
activity (study dosing)
6Saudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
Medication Related Information
Required dose
Medication Contraindication Major Drug Interactions Pregnancy
adjustment
- Body weight less than
50 kg (VTE prophylaxis):
Contraindicated
- Body weight less than
50 kg (VTE treatment):
Use with caution
- Body weight greater
than 100 kg (DVT
treatment): 10 mg subQ
daily (guideline dosing)
Argatroban - Hypersensitivity to o Apixaban: May enhance the anticoagulant effect of Anticoagulants. - Hepatic impairment Pregnancy
(second argatroban or to any o Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants (moderate to severe, Considerations
line)(when component of the o Edoxaban: May enhance the anticoagulant effect of Anticoagulants Child-Pugh class B and Information related to
fondaparinux is product o Hemin: Hemin may enhance the anticoagulant effect of Anticoagulants C) in heparin-induced Argatroban in
contraindicated) o Mifepristone: MiFEPRIStone may enhance the adverse/toxic effect of Anticoagulants. thrombocytopenia (HIT): pregnancy is limited.
- Major bleeding Specifically, the risk of bleeding may be increased. Avoid use or use a Use of parenteral
o Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. reduced dose. direct thrombin
o Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. inhibitors in pregnancy
o Urokinase: May enhance the anticoagulant effect of Anticoagulants. - In patients with bilirubin should be limited to
o Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. of greater than 1.5 those women who
(Refer to
mg/dL, use a dose of 0.5 have severe allergic
nomogram for
• To Consider therapy modification. to 1.2 mcg/kg/min. reactions to heparin,
doses)
o Desirudin: Anticoagulants may enhance the anticoagulant effect of Desirudin. Adjust aPTT to 1.5 to 3 including heparin-
Management: Discontinue treatment with other anticoagulants prior to desirudin times baseline induced
initiation. If concomitant use cannot be avoided, monitor patients receiving these thrombocytopenia,
combinations closely for clinical and laboratory evidence of excessive anticoagulation. - Hepatic impairment and who cannot
o Estrogen Derivatives: Carefully weigh the prospective benefits of estrogens against the (moderate to severe) in receive danaparoid
potential increased risk of procoagulant effects and thromboembolism. Use is considered (HIT): Initial dose 0.5 (Guyatt 2012).
contraindicated under some circumstances. Refer to related guidelines for specific mcg/kg/min; monitor
recommendations. aPTT closely and adjust
o Herbs (Anticoagulant/Antiplatelet Properties): Avoid such combinations when possible. If dosage as clinically
used concomitantly, increase diligence in monitoring for adverse effects (eg, bleeding, indicated. Achievement
bruising, altered mental status due to CNS bleeds). of steady state aPTT
o Progestins: Carefully weigh the prospective benefits of progestins against the potential levels may take longer
increased risk of procoagulant effects and thromboembolism. Use is considered and require more dose
contraindicated under some circumstances. Refer to related guidelines for specific adjustments in patients
recommendations. with hepatic impairment
7Saudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
Medication Related Information
Required dose
Medication Contraindication Major Drug Interactions Pregnancy
adjustment
compared to patients
with normal hepatic
function
- Hepatic impairment in
percutaneous coronary
intervention (PCI): Avoid
use with clinically
significant hepatic
disease or AST/ALT
levels 3 or more times
the ULN. In other
patients, titrate carefully
until the desired
level of anticoagulation
is achieved
- Critically ill patients
without organ failure in
HIT: Initial, 1
mcg/kg/min
- Critically ill patients
with multiple organ
failure or heart failure in
HIT: Initial, 0.5 to 0.6
mcg/kg/min
- Critically ill patients
with multiple organ
failure in HIT: Initial, 0.2
mcg/kg/min
- Heart failure, multiple
organ system failure, or
severe anasarca, or
post-cardiac surgery in
HIT: Initial, 0.5 to 1.2
mcg/kg/min
8Saudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
Medication Related Information
Required dose
Medication Contraindication Major Drug Interactions Pregnancy
adjustment
- Obesity (BMI up to 51
kg/m(2)): No dosing
adjustment required
when actual body
weight-based dosing to
target coagulation
response is utilized
Bivalirudin - Active major • Avoid combination. - Renal impairment Pregnancy
bleeding o Apixaban: May enhance the anticoagulant effect of Anticoagulants. (CrCl less than 30 Considerations
(Restricted for PCI o Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. mL/min): Reduce
patient with HIT) - Hypersensitivity to o Edoxaban: May enhance the anticoagulant effect of Anticoagulants. infusion rate to 1 Bivalirudin is used in
bivalirudin or its o Hemin: May enhance the anticoagulant effect of Anticoagulants. mg/kg/hr; monitor the conjunction with
components o Mifepristone: May enhance the adverse/toxic effect of Anticoagulants. anticoagulant status aspirin, which may
o Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of more frequently lead to maternal or
- Acute gastric or Omacetaxine. fetal adverse effects,
duodenal ulcer o Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. - Hemodialysis: Reduce especially during the
o Urokinase: May enhance the anticoagulant effect of Anticoagulants infusion rate to 0.25 third trimester. Use of
- Cerebral o Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. mg/kg/hr; no bolus dose parenteral direct
hemorrhage reduction is necessary thrombin inhibitors in
pregnancy should be
- Bacterial • To Consider therapy modification. - Obesity: The actual limited to those
endocarditis measured body weight women who have
o Desirudin: Discontinue treatment with other anticoagulants prior to desirudin (total body weight) severe allergic
- Diabetic or initiation. If concomitant use cannot be avoided, monitor patients receiving these should be used for dose reactions to heparin,
hemorrhagic combinations closely for clinical and laboratory evidence of excessive calculations, according including heparin-
retinopathy anticoagulation. to a retrospective review induced
o Estrogen Derivatives: Carefully weigh the prospective benefits of estrogens against in patients with heparin- thrombocytopenia,
- Proximal use of the potential increased risk of procoagulant effects and thromboembolism. Use is induced and who cannot
spinal/epidural considered contraindicated under some circumstances. Refer to related guidelines thrombocytopenia (HIT) receive danaparoid
anesthesia for specific recommendations. (n=135); in the obese (Guyatt 2012).
o Herbs (Anticoagulant/Antiplatelet Properties): Avoid such combinations when group, the mean total
possible. If used concomitantly, increase diligence in monitoring for adverse effects body weight was 105 +/-
(eg, bleeding, bruising, altered mental status due to CNS bleeds). 21.2 kg (range, 78 to
o Progestins: Carefully weigh the prospective benefits of progestins against the 176 kg) and mean BMI
potential increased risk of procoagulant effects and thromboembolism. Use is 37.7 +/- 6.7 kg/m(2)
considered contraindicated under some circumstances. Refer to related guidelines (range, 30.1 to 56.2
for specific recommendations. kg/m(2))
9Saudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
Medication Related Information
Required dose
Medication Contraindication Major Drug Interactions Pregnancy
adjustment
Apixaban - Active pathological - Renal impairment in
• Avoid combination. Based on placenta
bleeding nonvalvular atrial perfusion studies,
o Anticoagulants: Apixaban may enhance the anticoagulant effect of Anticoagulants.
fibrillation: 2.5 mg orally apixaban is expected
o Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants.
twice daily in patients to cross the placenta.
- Severe o Edoxaban: May enhance the anticoagulant effect of Anticoagulants.
with at least 2 of the
hypersensitivity (eg, o Hemin: May enhance the anticoagulant effect of Anticoagulants.
following characteristics, Information specific to
anaphylactic o Inducers of CYP3A4 (Strong) and P-glycoprotein: May decrease the serum
age 80 years or older, the use of apixaban in
reactions) to concentration of Apixaban
body weight 60 kg or pregnancy is limited
apixaban o MiFEPRIStone: May enhance the adverse/toxic effect of Anticoagulants.
less, or serum creatinine there is potential for
o Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine.
1.5 mg/dL (133 fetal bleeding or
o Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban.
mcmol/L) or higher subclinical placental
o St John's Wort: May decrease the serum concentration of Apixaban.
bleeding which may
o Urokinase: May enhance the anticoagulant effect of Anticoagulants.
- Renal impairment in increase the risk of
o Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants.
DVT prophylaxis miscarriage, preterm
following hip or knee delivery, fetal
replacement, or DVT or compromise, or
• To Consider therapy modification. stillbirth
pulmonary embolism
(PE) treatment or
o Antiplatelet Agents (P2Y12 Inhibitors): Carefully consider risks and benefits of this Data are insufficient to
secondary prophylaxis:
combination and monitor closely; Canadian labeling recommends avoiding prasugrel or evaluate the safety of
No dosage adjustment is
ticagrelor. direct acting oral
necessary
o Aspirin: Carefully consider risks and benefits of this combination and monitor closely. anticoagulants during
o CYP3A4 Inducers (Strong): Avoid concurrent use of apixaban with strong CYP3A4 pregnancy and use in
- Hepatic impairment
inducers whenever possible. Use of a strong CYP3A4 inducer with apixaban should be pregnant patients is
(mild, Child-Pugh class
strictly avoided in any patient who is using an agent (either the CYP3A4 inducer or a A): No dosage not recommended
third drug) that induces P-gp. adjustment necessary (ACOG 2018; Regitz-
o Estrogen Derivatives : Carefully weigh the prospective benefits of estrogens against the Zagrosek [ESC
potential increased risk of procoagulant effects and thromboembolism. Use is considered 2018]).
- Hepatic impairment
contraindicated under some circumstances. Refer to related guidelines for specific
(moderate, Child-Pugh
recommendations. class B): Dosing
o Fusidic Acid (Systemic): Consider alternatives to this combination when possible. recommendations are
Apixaban dose adjustments may be required when used with systemic fusidic acid. not provided, as the
Patients using this combination should be monitored extra closely.
impact on the
o Herbs (Anticoagulant/Antiplatelet Properties): Avoid such combinations when possible. If coagulation cascade
used concomitantly, increase diligence in monitoring for adverse effects (eg, bleeding, and its relationship to
bruising, altered mental status due to CNS bleeds). efficacy and bleeding is
o Inhibitors of CYP3A4 (Strong) and P-glycoprotein : US labeling recommends a 50%
not clearly understood in
apixaban dose reduction in patients who would otherwise receive 5 or 10 mg twice daily,
patients with moderate
and avoiding in patients who would otherwise receive 2.5 mg twice daily. Canadian impairment
labeling lists any combined use as contraindicated.
10Saudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
Medication Related Information
Required dose
Medication Contraindication Major Drug Interactions Pregnancy
adjustment
o Naproxen: A comprehensive risk to benefit assessment should be done for all patients - Hepatic impairment
before any concurrent use of apixaban and naproxen. If combined, monitor patients extra (severe, Child-Pugh
closely for signs and symptoms of bleeding. class C): Not
o Nonsteroidal Anti-Inflammatory Agents (Nonselective): A comprehensive risk to benefit recommended
assessment should be done for all patients before any concurrent use of apixaban and
nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra - Dialysis in DVT
closely for signs and symptoms of bleeding prophylaxis following hip
o Progestins: Carefully weigh the prospective benefits of progestins against the potential or knee replacement, or
increased risk of procoagulant effects and thromboembolism. Use is considered treatment or secondary
contraindicated under some circumstances. Refer to related guidelines for specific prophylaxis of DVT or
recommendations. pulmonary embolism
(PE): No dosage
adjustment is necessary
- Hemodialysis in stroke
prevention: In a
pharmacokinetics study,
2.5 mg twice daily
resulted in drug
exposure comparable to
5 mg twice daily in
patients with preserved
renal function
- Geriatric in nonvalvular
atrial fibrillation: 2.5 mg
orally twice daily in
patients with at least 2 of
the following
characteristics, age 80
years or older, body
weight 60 kg or less, or
serum creatinine 1.5
mg/dL (133 mcmol/L) or
higher
- Body weight 60 kg or
less in nonvalvular atrial
fibrillation: 2.5 mg orally
twice daily in patients
11Saudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
Medication Related Information
Required dose
Medication Contraindication Major Drug Interactions Pregnancy
adjustment
with at least 2 of the
following characteristics,
age 80 years or older,
body weight 60 kg or
less, or serum creatinine
1.5 mg/dL (133
mcmol/L) or higher
- Combined P-
glycoprotein and strong
CYP3A4 inhibitor (eg,
ketoconazole,
itraconazole, ritonavir):
Decrease dosage by
50% for patients
receiving apixaban
doses greater than 2.5
mg orally twice daily;
avoid coadministration in
patients already
receiving apixaban 2.5
mg twice daily
Warfarin - Blood dyscrasias • Avoid combination. - Renal impairment: No
adjustment necessary;
monitor INR more
- Cerebral o Hemin: May enhance the anticoagulant effect of Anticoagulants.
frequently in patients Use is contraindicated
aneurysms o MiFEPRIStone : May enhance the adverse/toxic effect of Vitamin K Antagonists. with compromised renal during pregnancy
o Omacetaxine : Anticoagulants may enhance the adverse/toxic effect of function to maintain INR except in patients with
Omacetaxine. within the therapeutic mechanical heart
- CNS hemorrhage
o Oxatomide: May enhance the anticoagulant effect of Vitamin K Antagonists. range valves who are at high
o Streptokinase: May enhance the anticoagulant effect of Vitamin K Antagonists. risk for
- Dissecting aorta o Tamoxifen : May increase the serum concentration of Vitamin K Antagonists. thromboembolism; use
- Geriatric: Consider
is also contraindicated
o Urokinase: May enhance the anticoagulant effect of Anticoagulants. using lower initial and
in patients with
- Eclampsia, o Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. maintenance dosage
threatened abortion,
preeclampsia,
- Asian patients: eclampsia, or
threatened abortion
Consider using lower preeclampsia.
initial and maintenance
- Gastrointestinal,
genitourinary, or • To Consider therapy modification.
dosage
respiratory tract
12Saudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
Medication Related Information
Required dose
Medication Contraindication Major Drug Interactions Pregnancy
adjustment
ulcerations or overt o Allopurinol: Monitor for increased prothrombin times (PT)/therapeutic effects of oral - INR; single out of
bleeding anticoagulants if allopurinol is initiated/dose increased, or decreased effects if range value, below or
allopurinol is discontinued/dose decreased. Reductions in coumarin dosage will above the therapeutic Use of warfarin during
likely be needed. INR by 0.5 or less, the first trimester may
-Hemorrhagic
tendencies o Amiodarone: Monitor patients extra closely for evidence of increased anticoagulant continue current warfarin be considered if the
effects if amiodarone is started. Consider empiric reduction of 30% to 50% in dose and test INR within therapeutic INR can
warfarin dose, though no specific guidelines on dose adjustment have been 1 to 2 weeks be achieved with a
- Hypersensitivity to published. dose ≤5 mg/day.
warfarin or any o Androgens: Monitor for increased effects of vitamin K antagonists if an androgen is - Bariatric surgery Alternately, adjusted-
component of the initiated/dose increased, or decreased effects if androgen is discontinued/dose (Roux-en-Y gastric dose low molecular
product decreased. Significant reductions in vitamin K antagonist dose are likely required. bypass or sleeve weight heparin or
o Barbiturates: Monitor INR more closely. Anticoagulant dose increases of 30% to gastrectomy): May adjusted-dose heparin
60% may be needed after a barbiturate is initiated or given at an increased dose. require approximately may be used until after
- Major regional or the first trimester,
Anticoagulant dose decreases may be needed following barbiturate discontinuation 25% reduction in daily
lumbar block when therapy can be
or dose reduction. dosage in the
anesthesia changed to warfarin, if
postoperative period
o CarBAMazepine: Monitor for decreased INR and effects of vitamin K antagonists if
required. Warfarin
carbamazepine is initiated/dose increased, or increased INR and effects if
- Malignant - Discontinuing therapy: should be
carbamazepine is discontinued/dose decreased. Vitamin K antagonist dose
hypertension Abrupt discontinuation is discontinued and
adjustments will likely be required.
suggested rather than changed to heparin at
o Cholestyramine Resin: Separate the administration of vitamin K antagonists and
gradual tapering of the least 1 week prior to
- Pericarditis and cholestyramine by at least 3 to 4 hours. Monitor patients closely for reduced vitamin delivery (ACC/AHA
dose (ACCP guidelines)
pericardial effusion K antagonist effects (eg, decreased INR, thrombosis) when these agents are [Otto 2021]). Consult
combined.
- Postpartum: Women current
- Pregnancy, except
o Cimetidine: Avoid coadministration of cimetidine and vitamin K antagonists. If who require more than 6 recommendations for
unavoidable, monitor for increased effects of vitamin K antagonists when cimetidine weeks of postpartum appropriate use in
in pregnant women
is initiated/dose increased, or decreased effects if cimetidine is discontinued/dose anticoagulation may be pregnancy.
with mechanical
decreased. initiated on warfarin
heart valves, who
are at high risk of o Desirudin: Discontinue treatment with other anticoagulants prior to desirudin (initial dose, 5 mg daily
thromboembolism initiation. If concomitant use cannot be avoided, monitor patients receiving these for 2 days, then adjusted
combinations closely for clinical and laboratory evidence of excessive per INR) and bridged
anticoagulation. with adjusted-dose low-
- Recent or potential o Enzalutamide: Avoid concurrent use of vitamin K antagonists and enzalutamide molecular-weight
surgery of central when possible. If combined, monitor for reduced vitamin K antagonist effects (ie, heparin (LMWH) or
nervous system or decreased INR, thrombosis) and increase vitamin K antagonist doses as needed. unfractionated heparin
eye o Estrogen Derivatives : Carefully weigh the prospective benefits of estrogens against (UFH) until INR is in the
the potential increased risk of procoagulant effects and thromboembolism. Use is therapeutic range of 2 to
- Recent or potential considered contraindicated under some circumstances. Refer to related guidelines 3 for 2 days, or a direct
traumatic surgery for specific recommendations. oral anticoagulant if not
breastfeeding. For
13Saudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
Medication Related Information
Required dose
Medication Contraindication Major Drug Interactions Pregnancy
adjustment
resulting in large o Estrogen Derivatives (Contraceptive): Avoid coadministration of estrogen- women with mechanical
open surface containing contraceptives and vitamin K antagonists. Consider nonhormonal heart valves, warfarin
methods of contraception in patients requiring vitamin K antagonists. If combined, can be resumed 24
monitor for changes in coagulation status. hours after delivery, with
- Spinal puncture
and other o Ethotoin: Anticoagulant dose adjustment will likely be necessary when ethotoin is overlapping IV UFH (or
initiated or discontinued. Monitor patients extra closely (INR and signs/symptoms of LMWH) until therapeutic
procedures with
bleeding) when using this combination. on warfarin
potential for
uncontrollable o Fenofibrate and Derivatives: Monitor for signs and symptoms of bleeding, and
increase INR monitoring in patients taking warfarin who are initiated on fenofibrate - Pregnancy, mechanical
bleeding
derivatives. Warfarin dose reductions will likely be required valve: Warfarin to goal
o Fenugreek: Seek alternatives to fenugreek in patients receiving vitamin K INR plus aspirin 75 mg
- Unsupervised and antagonists. Monitor patients receiving these combinations closely for increases in to 100 mg/day during
potentially INR and systemic effects of the vitamin K antagonist (particularly easy bruising and second and third
noncompliant bleeding). trimesters; during first
patients trimester, warfarin may
o Fibric Acid Derivatives: Consider reducing the oral anticoagulant dose by 25% to
be continued in patients
33% when initiating a fibric acid derivative. Monitor for toxic or reduced
who can achieve
anticoagulant effects if a fibric acid derivative is initiated/dose increased, or
therapeutic INR with
discontinued/dose decreased, respectively
doses of 5 mg/day or
o Fluconazole: Consider reducing the vitamin K antagonist dose by 10% to 20% if
less. Frequent
combined with fluconazole. Monitor for increased anticoagulant effects (ie,
monitoring required.
increased INR, bleeding) to guide further dose adjustments.
Discontinue warfarin and
o Fluorouracil Products: Monitor INR and for signs/symptoms of bleeding closely initiate continuous
when a fluorouracil product is combined with a vitamin K antagonist (eg, warfarin). infusion unfractionated
Anticoagulant dose adjustment will likely be necessary heparin prior to planned
o Fosphenytoin: Anticoagulant dose adjustment will likely be necessary when vaginal delivery
phenytoin is initiated or discontinued. Monitor patients extra closely (INR and (guideline dosing)
signs/symptoms of bleeding) when using this combination.
o Fusidic Acid (Systemic): Vitamin K antagonist dose adjustments may be required
when used with systemic fusidic acid. Patients using this combination should be
monitored extra closely for evidence of bleeding and to determine appropriate
dose.
o Ginkgo Biloba: Consider avoiding the use of this combination of agents. Monitor for
signs and symptoms of bleeding if vitamin K antagonists and Ginkgo biloba are
used concomitantly.
o Glutethimide: Consider avoiding glutethimide in patients receiving vitamin K
antagonists. Monitor for reduced anticoagulant effects if glutethimide is
initiated/dose increased or increased effects if glutethimide is discontinued/dose
decreased.
14Saudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
Medication Related Information
Required dose
Medication Contraindication Major Drug Interactions Pregnancy
adjustment
o Herbs (Anticoagulant/Antiplatelet Properties): Avoid such combinations when
possible. If used concomitantly, increase diligence in monitoring for adverse effects
(eg, bleeding, bruising, altered mental status due to CNS bleeds).
o Imatinib: Consider using low-molecular-weight heparin or heparin instead of
warfarin. If warfarin and imatinib must be coadministrered, increase monitoring of
INR and for signs/symptoms of bleeding.
o Menatetrenone: Coadministration is not recommended. If concomitant use of
menatetrenone and vitamin K antagonists cannot be avoided, monitor coagulation
parameters, such as PT/INR.
o MetroNIDAZOLE (Systemic): Consider alternatives to concomitant therapy with
these agents. If concomitant therapy cannot be avoided, consider reducing the
dose of the vitamin K antagonist and monitor for increased INR/bleeding
o Miconazole (Topical): Avoid using any miconazole-containing preparation in
patients who are taking warfarin. If coadministration is unavoidable, consider
reducing warfarin dose 10% to 20% and monitor for increased warfarin effects (eg,
INR, bleeding).
o Nafcillin: Consider choosing an alternative antibiotic. Monitor for decreased
therapeutic effects and need for dose adjustments of oral anticoagulants if nafcillin
is initiated/dose increased, or increased effects if nafcillin is discontinued/dose
decreased.
o Nonsteroidal Anti-Inflammatory Agents (Nonselective): Consider alternatives to this
combination when possible. If the combination must be used, monitor coagulation
status closely and advise patients to promptly report any evidence of bleeding or
bruising
o Phenytoin: Anticoagulant dose adjustment will likely be necessary when phenytoin
is initiated or discontinued. Monitor patients extra closely (INR and signs/symptoms
of bleeding) when using this combination.
o Progestins : Carefully weigh the prospective benefits of progestins against the
potential increased risk of procoagulant effects and thromboembolism. Use is
considered contraindicated under some circumstances. Refer to related guidelines
for specific recommendations.
o Progestins (Contraceptive): When possible, concomitant hormonal contraceptives
and coumarin derivatives should be avoided in order to eliminate the risk of
thromboembolic disorders. Consider using an alternative, nonhormonal
contraceptive.
o Rifamycin Derivatives: Monitor for reduced anticoagulant effects (ie, decreased
INR, thromboembolic events) if a rifamycin derivative is initiated in a vitamin K
antagonist treated patient. Vitamin K antagonist dose adjustments will likely be
required.
15Saudi MoH Protocol for
Vaccine-Induced Thrombosis and Thrombocytopenia (VITT)
(Version 1), 17/04/2021
Medication Related Information
Required dose
Medication Contraindication Major Drug Interactions Pregnancy
adjustment
o Salicylates : Avoid as needed use of salicylates in patients taking vitamin K
antagonists. Aspirin (80 to 325 mg/day) may be used with warfarin for prevention of
cardiovascular events. If coadministering salicylates and vitamin K antagonists,
monitor for bledding.
o Sodium Zirconium Cyclosilicate: Separate the administration of sodium zirconium
cyclosilicate and warfarin by at least 2 hours. If simultaneous administration is
required, monitor for signs and symptoms of warfarin toxicity (eg, elevated INR,
bleeding).
o SORAfenib: Warfarin dose adjustment will likely be necessary. Increase frequency
of INR monitoring during sorafenib therapy (particularly when starting or stopping
therapy), and increase monitoring for signs and symptoms of bleeding.
o St John's Wort: Consider avoiding coadministration of St John's Wort and vitamin K
antagonists. If combined, monitor for decreased anticoagulant therapeutic effects
(eg, decreased INR, thromboembolic events) if St John's Wort is initiated/dose
increased.
o Sulfonamide Antibiotics: Consider reducing the vitamin K antagonist dose by 10%
to 20% prior to starting the sulfonamide antibiotic. Monitor INR closely to further
guide dosing.
References:
-UpToDate last access March 2021
-Micromedex last access March 2021
-https://www.ema.europa.eu/en/news/astrazenecas-covid-19-vaccine-ema-finds-possible-link-very-rare-cases-unusual-blood-clots-low-blood (Accessed on April 07, 2021).
-https://www.who.int/news/item/07-04-2021-interim-statement-of-the-covid-19-subcommittee-of-the-who-global-advisory-committee-on-vaccine-safety (Accessed on April 07,
2021).
-Greinacher, A. Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination, NEJM, April 9, 2021
-Schultz, N, Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination, NEJM, April 9,2021
- Pai, M. Vaccine-induced prothrombotic immune thrombocytopenia VIPIT following AstraZeneca COVID-19 vaccination. Science Briefs of the Ontario COVID-19 Science
Advisory Table. 2021;1(17). https://doi.org/10.47326/ocsat.2021.02.17.1.0
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