Factor VIII Indications & Dosing for adults

The hemophilic conditions are a group of related inherited bleeding disorders and include abnormalities of coagulation factors as well as platelet function

General Dosing Recommendation:

INDICATION	% OF NORMAL	DOSE
Minor hemorrhage	~20% to 40%	·      10-20 units/kg as a single dose ·      Mild superficial or early hemorrhages may respond to a single dose; ·      may repeat dose every 12-24 hours for 1-3 days until bleeding is resolved or healing achieved
Moderate hemorrhage/minor surgery	30% to 50%	·      15-25 units/kg ·      If needed, may continue with a maintenance dose of 10-15 units/kg every 8-12 hours.
Major to life-threatening hemorrhage	80% to 100%	·      Initial dose 40-50 units/kg ·      followed by a maintenance dose of 20-25 units/kg every 8-12 hours until threat is resolved
Major surgery	100% before surgery	·      50 units/kg given preoperatively ·      May repeat as necessary after 6-12 hours initially and for a total of 10-14 days until healing is complete. ·      Intensity of therapy may depend on type of surgery and postoperative regime
Bleeding prophylaxis		·      May be administered on a regular basis for bleeding prophylaxis. ·      Doses of 24-40 units/kg 3 times/week have been reported in patients with severe hemophilia to prevent joint bleeding

 

 Dosage based on desired factor VIII increase (%):

To calculate dosage needed based on desired factor VIII increase (%):

Body weight (kg) x 0.5 units/kg x desired factor VIII increase (%) = units factor VIII required

For example:

50 kg x 0.5 units/kg x 30 (% increase) = 750 units factor VIII 

Dosage based on expected factor VIII increase (%):

It is also possible to calculate the expected % factor VIII increase:

(# units administered x 2%/units/kg) divided by body weight (kg) = expected % factor VIII increase

For example:

(1400 units x 2%/units/kg) divided by 70 kg = 40%

references:
1. www.uptodate.com
2. lexicomp

When is it Indicated to Start Corticosteroids in COPD Exacerbations?

Rationale:

• Studies concluded that systemic (oral or intravenous) glucocorticoids reduced treatment failure
• increased the rate of improvement in lung function and symptoms
• more rapid increase in FEV₁, fewer withdrawals, and a significantly shorter hospital stay
• benefits of glucocorticoids appear to be greatest in the first 72 hours after administration

Outpatient exacerbations:

• small, but significant clinical effect
• Patients who received prednisone (40mg for 10 days) were less likely to return with increasing dyspnea within 30 days (27 versus 43 percent). In addition to a lower rate of relapse, prednisone therapy was associated with decreased dyspnea

Hospitalised Patients:

• Rate of treatment failure was about 10 percent lower
• Shorter hospital stay and more rapid improvement of FEV1
• No difference between efficacy of oral and IV

Adverse effect of short term therapy:

• Only hyperglycemia was more common in the glucocorticoid-treated groups
• Patients who received the eight-week course of glucocorticoids had a tendency to have more severe infections, particularly pneumonia
• Patients treated with short-term, high-dose glucocorticoids for septic shock have a significantly increased risk of secondary bacterial infection and an increased mortality

Selection criteria:

• Currently, no criteria have been established for deciding which patients benefit most from corticosteroid therapy.
• Thus, all patients without serious contraindications should receive systemic corticosteroids for severe exacerbations of COPD

	Severity of exacerbation Description Mild Can be controlled with an increase in dosage of regular medications Moderate Requires treatment with systemic corticosteroids or antibiotics Severe Requires hospitalization or evaluation in the emergency department

Duration:

• No more than two weeks of therapy are needed; shorter courses may achieve adequate outcomes but need further study.
• Extending the duration of therapy beyond 2 weeks and using higher doses does not confer additional benefits, but can increase the risk of short-term side effects such as hyperglycemia and insomnia
• If steroid therapy is continued for longer than 2 weeks, a tapering schedule should be employed to avoid hypothalamic-pituitary-adrenal axis suppression
• As a rough guide, full dose therapy (eg, prednisone 40 mg daily) is given for 5 to 14 days

Treatment:

• a compromise approach to dosing; administer one or more high doses (eg, methylprednisolone 80 to 125 mg) in the first 24 hours with rapid conversion to lower-dose therapy (prednisone 40 to 60 mg per day) if the patient is improving.
• IV glucocorticoids are typically administered to patients who present with a severe exacerbation, who respond poorly to oral glucocorticoids, unable to take oral medication, or who may have impaired absorption due to decreased splanchnic perfusion (eg, patients in shock).
•  A reasonable alternative is to use a regimen of prednisone or its equivalent in doses of 30 to 60 mg per day for the duration of therapy

futher reading:

References:

1. http://www.aafp.org/afp/2010/0301/p607.html
2. http://respiratory-research.com/content/15/1/38
3. http://www.patient.co.uk/doctor/acute-exacerbations-of-copd
4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2111219/
5. www.uptodate.com

Antibiotic use in Reactive Arthritis

Arthritis that arises following an infection (several days to weeks), although the pathogens cannot be cultured from the affected joints

Common causative agents:

• Panel of experts determined a specific list of gastrointestinal and urogenital pathogens that could be considered causative. These included Chlamydia trachomatis, Yersinia, Salmonella, Shigella, and Campylobacter.
• Escherichia coli, Clostridium difficile, and Chlamydia pneumoniae have since been added to the list
• Reactive arthritis has also been reported in patients with human immunodeficiency virus (HIV) infection, in which it is generally thought to be related to other infections to which patients have been exposed, rather than to HIV itself

Antibiotic:

• Antibiotics are not used to treat the arthritis specifically
• may be indicated for treatment of the underlying infection if there is evidence of ongoing genitourinary infection or carriage of potentially pathogenic organisms
• studies showed no difference compared to placebo in terms of remission

Enteric infection:

• antibiotics are not indicated for uncomplicated enteric infections
• patients with active enteric infections may require treatment. For example, therapy may be indicated in patients with severe gastrointestinal disease, in older adults, or in immunocompromised hosts
• oral fluoroquinolone (ciprofloxacin 500 mg twice daily, norfloxacin 400 mg twice daily, or levofloxacin 500 mg once daily) for three to five days. Azithromycin (500 mg PO once daily for three days) or erythromycin (500 mg PO twice daily for five days) are alternative agents, particularly if fluoroquinolone resistance is suspected

Genitourinary tract infection:

• patients with acute Chlamydia trachomatis infection of the genitourinary tract and their sexual partners should receive a standard antimicrobial treatment
• might prevent relapses of arthritis in patients with recurrent genitourinary tract symptoms alone
• azithromycin (1 gram single-dose therapy) with observed therapy when possible. Doxycycline (100 mg twice daily) can also be used in the nonpregnant patient for seven days

References:

1. www.uptodate.com

Prophylaxis for children in VUR

VUR: Vesicoureteral reflux (VUR) is the backflow of urine from the bladder into the upper urinary tract. Management of VUR has been based upon the premise that VUR predisposes patients to acute pyelonephritis.

Rationale:

• assumptions that use of continuous antibiotics results in sterile urine and the continued reflux of sterile urine does not cause renal damage, and the observation that reflux spontaneously resolves in most cases

Evidences:

• Several systemic reviews reporter no difference when compared to placebo
• However, more recent higher quality clinical trials have shown antibiotic prophylaxis reduces the risk of recurrent UTI in young children.

Choice of agents:

• Once daily dose is administered at bedtime
• The dose is ½ to ¼ of the usual therapeutic dose
• The following are single daily doses of commonly used antimicrobial agents:

DRUG	DOSE	RATIONALE
Trimethoprim-sulfamethoxazole or TMP alone	Dosing is based on TMP at 2 mg/kg	Less likely to have recurrent febrile or symptomatic UTI Did not reduce the incidence of renal scarring Increased risk of resistance increased risk of neonatal hyperbilirubinemia
Nitrofurantoin	1 to 2 mg/kg	increased risk of neonatal hyperbilirubinemia
Cephalexin	10 mg/kg	Not generally recommended because of increased risk of resistant organism Only for infants below 2 month, because of adverse effects of sulfanamides, TMP or nitrofurantoin
Ampicillin	20 mg/kg
Amoxicillin	10 mg/kg

Duration:

• Indications of when to discontinue medical therapy are uncertain
• Some experts will only discontinue therapy when the VCUG is negative. Others will discontinue therapy in older children or adolescents with grade I reflux who have been infection free for a year or so
• Long-term follow-up includes annual assessment of linear growth, measurement of blood pressure, and urinalysis

References:
1. www.uptodate.com