In this episode I’ll:
1. Discuss an article recommending DDAVP for intracranial hemorrhage from anti-platelet agents
2. Answer the drug information question: “What should I use to treat a DVT in a patient on CRRT with a recent history of HIT?”
3. Share a resource I use to get an early clue on the identification of organisms in cultures
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Lead author: Jennifer A. Frontera
Published in the journal Neurocritical Care in December 2015
The article provides a comprehensive review of the available reversal strategies for intracranial hemorrhage (ICH) due to antithrombotics. In this episode I’ll highlight the article’s recommendations on when to give desmopressin (DDAVP) for ICH.
Desmopressin is an analog of vasopressin but has little vasopressor activity. Desmopressin causes the release of von Willebrand factor and increases platelet adhesion.
In uremic patients desmopressin normalizes hemostasis and reduces bleeding time. In uremic patients exposed to aspirin desmopressin has been found to improve platelet function. DDAVP has also been shown to significantly reduce blood loss and improve thrombus formation in cardiac surgery patients exposed to aspirin pre-operatively.
DDAVP for anti-platelet reversal in intracranial hemorrhage has been reported in a handful of studies, usually at a dose of 0.4 mcg/kg IV. It appears DDAVP can stabilize platelet function, but the duration of effect is influenced by the amount and frequency of anti-platelet dosing. Repeat dosing of DDAVP may be required in some patients.
Side effects of DDAVP are considered mild and include facial flushing, edema, fluid overload, and hyponatremia. Rarely cerebrovascular or cardiac thrombosis has been reported.
Because of the low risk of serious side effects, the relatively low cost, and the suggestion of benefit the authors state:
We suggest consideration of a single dose of desmopressin (DDAVP) in intracranial hemorrhage (0.4 mcg/kg IV) associated with aspirin/COX-1 inhibitors or ADP receptor inhibitors. In patients deemed appropriate (e.g., those undergoing a neurosurgical procedure), DDAVP can be used in addition to platelet transfusion. (Conditional recommendation, low-quality evidence)
Drug information question
Q: What should I use to anticoagulate a patient on CRRT with a recent history of heparin induced thrombocytopenia (HIT)?
PharmacyJoe-ism #2 is “The first question is not the real question” and this drug information question illustrates that concept perfectly. Before I could give the provider an answer I had to ask them several questions:
How long ago did the patient have HIT? Why and for how long do they need to be anticoagulated?
The answer to the drug information question depends on patient specific factors:
A patient with a history of HIT within the past 3 months has a very high risk of fatal thrombosis if they are re-exposed to heparin. Patients who have a more remote history of HIT may tolerate heparin. Depending on the indication for use the risk may be worth taking.
HIT antibodies have two unique properties:
1. The HIT antibody is temporary, with a median time to disappearance of 50 to 80 days.
2. Patients with a prior history of HIT who are antibody negative have an “amnestic” immune response (meaning the patient is not sensitized and will need 4 days of re-exposure to heparin before possibly reacting again).
Because of these unique properties, it may be possible to re-expose a patient with a previous history of HIT to heparin for 4 days without precipitating a second episode of acute HIT. There are no prospective clinical trials that evaluate this concept.
Considering these unique properties of HIT antibodies in a risk:benefit analysis, the authors of the CHEST Guidelines on the Prevention and Treatment of HIT have the following recommendations:
In patients with a history of HIT in whom heparin antibodies have been shown to be absent who require cardiac surgery, we suggest the use of heparin (short-term use only) over nonheparin anticoagulants (Grade 2C).
In patients with a history of HIT in whom heparin antibodies are still present who require cardiac surgery, we suggest the use of nonheparin anticoagulants over heparin or LMWH (Grade 2C).
In patients with a history of HIT who require cardiac catheterization or PCI, the recommended treatment is bivalirudin or argatroban (Grade 2B).
In patients with a past history of HIT who have acute thrombosis (not related to HIT) and normal renal function, we suggest the use of fondaparinux at full therapeutic doses until transition to VKA can be achieved (Grade 2C).
A: The patient that I was asked this question about was on continuous renal replacement therapy (CRRT), needed treatment for a DVT, and had HIT 70 days ago. I recommended using argatroban to bridge the patient to oral warfarin therapy.
The resource for this episode is two charts from wikipedia.org that illustrate the steps in the classification of gram positive and gram negative bacteria.
Understanding the steps the laboratory takes to identify pathogens from cultures is occasionally useful to justify broadening or narrowing empiric antibiotic therapy before culture results are finalized.
For example, if a patient has a gram negative bacilli growing that is not fermenting lactose, pseudomonal coverage should be considered until the culture results are finalized.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.