Dose calculation

Typical initial targets and doses, if no FVIII inhibitor

Repeat dosing and monitoring

• Recheck FVIII activity where available, usually including a post-infusion level and trough levels for significant bleeds or surgery.
• A common maintenance approach is about half the initial dose every 8-12 hours, then adjust to the measured FVIII level, clinical response, product recovery, and site of bleeding.
• For prolonged treatment, one reference suggests 25-30 IU/kg IV every 12 hours with dose adjustment according to peak and trough FVIII levels. Mild hemorrhage often resolves after 1-3 doses targeting 30%-50%; major trauma/surgery generally requires maintaining levels above 80% initially. The Washington Manual of Medical Therapeutics, p. 768.
• Extended-half-life FVIII products have different dosing intervals. Follow that product's prescribing information and the patient's hemophilia treatment plan.

Administration steps

1. Treat first when a serious hemophilia-related bleed is suspected. Do not delay replacement for imaging in possible intracranial, neck/throat, abdominal, iliopsoas, or major trauma bleeding.
2. Confirm the person has hemophilia A, their usual FVIII product, last dose, baseline severity, and inhibitor status.
3. Reconstitute the prescribed product using its supplied diluent and device under aseptic technique.
4. Give by peripheral IV access at the product-specific permitted injection/infusion rate.
5. Record product name, lot number, units given, time, clinical site of bleeding, and post-dose FVIII level if checked.
6. Monitor clinical hemostasis, hemoglobin when relevant, and FVIII activity. Lack of expected response should prompt urgent evaluation for an FVIII inhibitor.

Important exceptions

• Known or suspected FVIII inhibitors: do not assume ordinary FVIII doses will work. Contact a hemophilia treatment center urgently. Low-responding inhibitors may sometimes be managed with monitored higher-dose FVIII; high-responding inhibitors generally need bypassing therapy such as recombinant factor VIIa.
• Emicizumab prophylaxis: standard aPTT and one-stage FVIII assays can give misleading results. A chromogenic assay using bovine reagents is generally needed to measure FVIII accurately.
• Mild hemophilia A with a documented desmopressin response: DDAVP may be an alternative for selected minor bleeds or minor procedures, but not for life-threatening bleeds. The Washington Manual of Medical Therapeutics, p. 768.

Probable diagnoses

1. Peptic ulcer bleed - gastric or duodenal ulcer, often related to H. pylori, NSAIDs, aspirin, or anticoagulants. This is the commonest cause.
2. Esophageal or gastric varices - especially with cirrhosis, portal hypertension, jaundice, ascites, alcohol-related liver disease, or splenomegaly.
3. Erosive gastritis/duodenitis or esophagitis - alcohol, NSAIDs, aspirin, severe physiological stress.
4. Mallory-Weiss tear - hematemesis after repeated retching or vomiting.
5. Less common: malignancy, Dieulafoy lesion, vascular ectasia, swallowed blood from epistaxis/oral bleeding.

• Painless hematemesis plus cirrhosis/portal-hypertension signs: presume variceal bleeding.
• Epigastric pain, NSAID/aspirin use, prior ulcer: peptic-ulcer bleeding.
• Blood after forceful vomiting/retching: Mallory-Weiss tear.
• A raised BUN:creatinine ratio supports an upper-GI source because absorbed digested blood increases urea. Frameworks for Internal Medicine, p. 217.

Immediate evaluation and stabilization

1. ABC approach

• Assess airway, breathing, circulation, mental status.
• Give oxygen if hypoxemic.
• Early airway protection/intubation if massive active hematemesis, reduced consciousness, inability to protect the airway, or severe shock.
• Keep NPO.
• Two large-bore IV cannulas, continuous BP/heart-rate/oxygen monitoring.
• Call gastroenterology/endoscopy and senior emergency/medical support early.

2. Resuscitation

• Start isotonic crystalloid if hypotensive, while preparing blood products.
• Send:
  • CBC with platelets
  • Group and crossmatch
  • PT/INR, aPTT, fibrinogen
  • Urea, creatinine, electrolytes, liver tests
  • Glucose
  • Venous/arterial blood gas and lactate if shocked
• Perform abdominal examination and digital rectal examination for melena.
• Take a focused history: quantity/colour of blood, melena, syncope, NSAIDs/aspirin, anticoagulants, alcohol, liver disease, previous ulcer/varices, vomiting/retching.

3. Blood products and correction of coagulation

• Use a generally restrictive red-cell transfusion approach, usually transfusing when Hb is <7 g/dL (70 g/L) in stable patients.
• Consider a higher threshold, commonly <8 g/dL, with ischemic heart disease, significant cardiovascular disease, ongoing shock, or massive hemorrhage.
• Correct clinically significant thrombocytopenia/coagulopathy in consultation with specialists, especially if active bleeding or a procedure is needed.
• If the patient uses anticoagulants, withhold and consider appropriate reversal for severe/life-threatening bleeding.

Risk stratification

Specific initial treatment

If non-variceal bleed is likely or diagnosis is uncertain

• IV PPI: e.g., pantoprazole 80 mg IV bolus, then 8 mg/hour continuous IV infusion for 72 hours after endoscopic hemostasis.
• High-dose intermittent IV or oral PPI twice daily can be used where appropriate according to local protocol.
• Consider IV erythromycin before endoscopy in significant bleeding to clear the stomach, if no contraindication.
• Stop NSAIDs. Review aspirin and anticoagulants with the treating team.

If variceal bleeding is suspected

• Octreotide 50 micrograms IV bolus, then 50 micrograms/hour IV infusion.
• Ceftriaxone 1 g IV every 24 hours, typically for up to 7 days, unless an alternative antibiotic is indicated.
• Urgent endoscopy with variceal band ligation if esophageal varices are found.
• This combination of vasoactive therapy, antibiotic prophylaxis, resuscitation and band ligation is standard acute management. Goldman-Cecil Medicine, “Varices and Variceal Bleeding,” p. 2358.

If the patient has hemophilia A / factor VIII deficiency

Definitive diagnosis and treatment

• Injection therapy, usually dilute epinephrine only in combination with another method
• Hemostatic clips
• Thermal coagulation
• Hemostatic powder or over-the-scope clip in selected refractory cases
• Variceal band ligation for esophageal varices

1. Repeat therapeutic endoscopy.
2. Transcatheter arterial embolization if non-variceal endoscopic control fails.
3. Surgery if embolization is unavailable or unsuccessful.

After hemostasis

• Test for and eradicate H. pylori if peptic ulcer disease is found.
• Continue PPI therapy according to endoscopic risk category.
• Avoid NSAIDs where possible. If essential, use gastroprotection.
• For varices: arrange secondary prophylaxis with a nonselective beta-blocker plus repeat band ligation.

• Aspirin: use 162-325 mg chewed, even if the patient takes low-dose aspirin chronically, unless true aspirin allergy or active major bleeding.
• Clopidogrel: do not give 600 mg if fibrinolysis is planned. For primary PCI it is commonly 600 mg, though ticagrelor or prasugrel may be preferred in suitable PCI patients.
• Atorvastatin: give 80 mg as early as possible unless there is a significant contraindication such as previous serious statin toxicity or active severe liver disease.
• STEMI also requires immediate ECG monitoring, IV access, anticoagulation and rapid primary PCI when available. Do not delay reperfusion for medications.