UMEM Educational Pearls - By To-Lam Nguyen

Since Christmas is coming up, let's talk about Hemophilia A (factor VIII deficiency) and Hemophilia B (factor IX deficiency, also known as Christmas disease)

Deficiencies in Factors VIII and IX are the most common severe inherited bleeding disorders.

Pathophysiology: 

  • Factors VIII and IX are required for activation of factor X.
  • In patients with Hemophilia A (factor VIII deficiency) or Hemophilia B (factor IX deficiency, also known as Christmas disease), after an injury, clot formation is delayed. 
  • Inadequate thrombin generation leads to failure to form a tightly crosslinked fibrin clot to support platelet plug, which leads to easy bleeding.
  • Clot that is formed may be friable and rebleeding occurs during physiologic lysis of clots or with minimal new trauma

Clinical Manifestations:

  • 2% of neonates with hemophilia have intracranial hemorrhages
  • 30% of male infants with hemophilia bleed with circumcision
  • Continued bleeding from umbilical stump in neonate
  • In absence of positive family history (hemophilia has high rate of spontaneous mutation), hemophilia may go undiagnosed in a newborn
  • Easy bruising, intramuscular hematomas, and hemarthroses (hallmark for hemophilic bleeding) begin when child begins to cruise
  • Bleeding from minor traumatic lacerations of the mouth (e.g. torn frenulum) can persist for hours or days
  • Iliopsoas hemorrhage: patient may lose large volumes of bleed into the muscle, leading to hypovolemic shock, with only a vague complaint of area of referred pain in the groin. Hip is held in a flexed, internally rotated position, due to irritation of the iliopsoas.
    • Confirmed on CT or US
    • Clinically unable to extend hip
  • Hemarthrosis rare in patients with acquired hemophilia

Lab findings and diagnosis

  • Reduced levels of factor VIII or factor IX will cause higher PTT 
  • PTT is usually 2-3x upper limit of normal in patients with severe hemophilia.
  • Platelet count, bleeding time, prothrombin time, and thrombin time are all normal
  • If PTT is not corrected after administration of factor VIII or IX, an inhibitor may be present.
    • 25-35% of patients with hemophilia who received infusions of factor VIII or factor IX, a factor specific antibody may develop (inhibitor)

Genetics

  • Hemophilia occurs in 1:5000 males, with 85% having factor VIII deficiency and 10-15% having factor IX deficiency
  • No apparent racial predilection, appearing in all ethnic groups

 

Classification

  • Severe hemophilia: <1% activity of specific clotting factor and bleeding is often spontaneous
  • Moderate hemophilia: 1-5% activity and require mild

trauma to induce bleeding

  • Mild hemophilia: >5% activity and can go many years before diagnosis and usually require significant trauma to induce bleeding.

Treatment

  • Ask patient or family if they brought their dosing information with them or their factor replacement with them. In many cases, they have it!
  • For life-threatening or major hemorrhages, dose should aim to achieve levels of 100% activity
    • Hemophilia A: 50U/kg recombinant Factor VIII (each U/kg of factor VIII in hemophilia A increases factor by 2%)
    • Hemophilia B: 100U/kg recombinant Factor IX (each U/kg of factor VIII in hemophilia A increases factor by 1%)
    • Aim for 50% correction in moderate bleeds and 100% correction in severe bleeds
    • If you don’t have factor-specific products:
      • Hemophilia A
        • can give 1U cryoprecipitate (~80U of factor VIII) or try PCC (as it contains factors II, VII, IX, and X)
        • activated PCC (FEIBA) 75-100U/kg
      • Hemophilia B
        • FFP NO LONGER RECOMMENDED (volume of FFP required has high risk of volume overload)
        • Cryoprecipitate does NOT contain factor IX, so will not work.
  • For acute bleeding in patients with mild hemophilia A:
    • Can give DDAVP: increases factor VIII by 3-5x by encouraging release of endogenous factor VIII. Recommended dose: 0.3mcg/kg/dose IV
  • For mild bleeding:
    • TXA (clot stabilizer)
    • Desmopressin
    • Aminocaproic acid
  • If patient has inhibitors:
    • Hemophilia A: 
      • Activated PCC (75-100U/kg) (do NOT give if on patient is on emicizumab (Hemlibra) due to risk of thrombosis)
      • Recombinant factor VII 90mcg/kg
    • Hemophilia B:
      • Recombinant factor VII 90mcg/kg

 

Summary:

  • Aim for 50% correction in moderate bleeds and 100% correction in severe bleeds
  • Hemophilia A: 50U/kg recombinant Factor VIII (each U/kg of factor VIII in hemophilia A increases factor by 2%)
  • Hemophilia B: 100U/kg recombinant Factor IX (each U/kg of factor VIII in hemophilia A increases factor by 1%)
  • Treatment if patient has no inhibitors:
    • Hemophilia A: 
      • Severe bleed: Give full dose factor XIII (50U/kg), even if the patient is on prophylaxis
      • Mild bleeds: factor XIII replacement (25U/kg), TXA, DDAVP, aminocaproic acid
    • Hemophilia B: 
      • Severe bleed: Give full dose factor IX (100U/kg), even if the patient is on prophylaxis
      • Mild bleeds: factor IV replacement (50U/kg), TXA, aminocaproic acid
  • Treatment if patient has inhibitors:
    • Hemophilia A: 
      • Activated PCC (75-100U/kg) (do NOT give if on patient is on emicizumab (Hemlibra) due to risk of thrombosis)
      • Recombinant factor VII 90mcg/kg
    •  Hemophilia B:
      • Recombinant factor VII 90mcg/kg

 

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Since Christmas is coming up, let's talk about Hemophilia A (factor VIII deficiency) and Hemophilia B (factor IX deficiency, also known as Christmas disease)

Deficiencies in Factors VIII and IX are the most common severe inherited bleeding disorders.

Pathophysiology:

  • Factors VIII and IX are required for activation of factor X.
  • In patients with Hemophilia A (factor VIII deficiency) or Hemophilia B (factor IX deficiency, also known as Christmas disease), after an injury, clot formation is delayed.
  • Inadequate thrombin generation leads to failure to form a tightly crosslinked fibrin clot to support platelet plug, which leads to easy bleeding.
  • Clot that is formed may be friable and rebleeding occurs during physiologic lysis of clots or with minimal new trauma

Clinical Manifestations:

  • 2% of neonates with hemophilia have intracranial hemorrhages
  • 30% of male infants with hemophilia bleed with circumcision
  • Continued bleeding from umbilical stump in neonate
  • In absence of positive family history (hemophilia has high rate of spontaneous mutation), hemophilia may go undiagnosed in a newborn
  • Easy bruising, intramuscular hematomas, and hemarthroses (hallmark for hemophilic bleeding) begin when child begins to cruise
  • Bleeding from minor traumatic lacerations of the mouth (e.g. torn frenulum) can persist for hours or days
  • Iliopsoas hemorrhage: patient may lose large volumes of bleed into the muscle, leading to hypovolemic shock, with only a vague complaint of area of referred pain in the groin. Hip is held in a flexed, internally rotated position, due to irritation of the iliopsoas.
    • Confirmed on CT or US
    • Clinically unable to extend hip
  • Hemarthrosis rare in patients with acquired hemophilia

Lab findings and diagnosis

  • Reduced levels of factor VIII or factor IX will cause higher PTT
  • PTT is usually 2-3x upper limit of normal in patients with severe hemophilia.
  • Platelet count, bleeding time, prothrombin time, and thrombin time are all normal
  • If PTT is not corrected after administration of factor VIII or IX, an inhibitor may be present.
    • 25-35% of patients with hemophilia who received infusions of factor VIII or factor IX, a factor specific antibody may develop (inhibitor)

Genetics

  • Hemophilia occurs in 1:5000 males, with 85% having factor VIII deficiency and 10-15% having factor IX deficiency
  • No apparent racial predilection, appearing in all ethnic groups

 

Classification

  • Severe hemophilia: <1% activity of specific clotting factor and bleeding is often spontaneous
  • Moderate hemophilia: 1-5% activity and require mild

trauma to induce bleeding

  • Mild hemophilia: >5% activity and can go many years before diagnosis and usually require significant trauma to induce bleeding.

Treatment

  • Ask patient or family if they brought their dosing information with them or their factor replacement with them. In many cases, they have it!
  • For life-threatening or major hemorrhages, dose should aim to achieve levels of 100% activity
    • Hemophilia A: 50U/kg recombinant Factor VIII (each U/kg of factor VIII in hemophilia A increases factor by 2%)
    • Hemophilia B: 100U/kg recombinant Factor IX (each U/kg of factor VIII in hemophilia A increases factor by 1%)
    • Aim for 50% correction in moderate bleeds and 100% correction in severe bleeds
    • If you don’t have factor-specific products:
      • Hemophilia A
        • can give 1U cryoprecipitate (~80U of factor VIII) or try PCC (as it contains factors II, VII, IX, and X)
        • activated PCC (FEIBA) 75-100U/kg
      • Hemophilia B
        • FFP NO LONGER RECOMMENDED (volume of FFP required has high risk of volume overload)
        • Cryoprecipitate does NOT contain factor IX, so will not work.
  • For acute bleeding in patients with mild hemophilia A:
    • Can give DDAVP: increases factor VIII by 3-5x by encouraging release of endogenous factor VIII. Recommended dose: 0.3mcg/kg/dose IV
  • For mild bleeding:
    • TXA (clot stabilizer)
    • Desmopressin
    • Aminocaproic acid
  • If patient has inhibitors:
    • Hemophilia A:
      • Activated PCC (75-100U/kg) (do NOT give if on patient is on emicizumab (Hemlibra) due to risk of thrombosis)
      • Recombinant factor VII 90mcg/kg
    • Hemophilia B:
      • Recombinant factor VII 90mcg/kg

 

Summary:

  • Aim for 50% correction in moderate bleeds and 100% correction in severe bleeds
  • Hemophilia A: 50U/kg recombinant Factor VIII (each U/kg of factor VIII in hemophilia A increases factor by 2%)
  • Hemophilia B: 100U/kg recombinant Factor IX (each U/kg of factor VIII in hemophilia A increases factor by 1%)
  • Treatment if patient has no inhibitors:
    • Hemophilia A:
      • Severe bleed: Give full dose factor XIII (50U/kg), even if the patient is on prophylaxis
      • Mild bleeds: factor XIII replacement (25U/kg), TXA, DDAVP, aminocaproic acid
    • Hemophilia B:
      • Severe bleed: Give full dose factor IX (100U/kg), even if the patient is on prophylaxis
      • Mild bleeds: factor IV replacement (50U/kg), TXA, aminocaproic acid
  • Treatment if patient has inhibitors:
    • Hemophilia A:
      • Activated PCC (75-100U/kg) (do NOT give if on patient is on emicizumab (Hemlibra) due to risk of thrombosis)
      • Recombinant factor VII 90mcg/kg
    •  Hemophilia B:
      • Recombinant factor VII 90mcg/kg

 

 

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- Magnets move through the GI tract at different rates and become lodged in adjacent loops of intestine. Adjacent bowel segments can stick together when the magnets attract each other through the bowel walls which can cause obstruction, perforation, fistula formation, and necrotic bowel.

- Obtain xray to identify ingested metallic object(s)

- Any object lodged in the esophagus should be emergently removed by a pediatric gastroenterologist.

- Once an object is past the stomach and beyond the reach of endoscopy, affected patients need to be watched carefully for signs of obstruction or peritonitis, either occurrence requiring the prompt consultation of a pediatric surgeon.

- Enhancement of magnet movement through the GI  tract may be aided by a laxative such as polyethylene glycol, but there is no clear data that this approach speeds the passage of the magnet. There is no clear guidance on how frequently to obtain abdominal radiographs to determine movement or passage of ingested magnets.

- More frequently lodge in esophagus due to seize and cause electric urn on contact

- Complications include perforation or fistula formation

- Honey or liquid ulcer medication carafate can slow extent of esophageal injury

- Current recommendations from National Button Battery Hotline: caregiver to give 2 teaspoons of honey every 10 minutes while en route to hospital

- Causes caustic contact to vocal cords, which leads to acute laryngospasm 

- Airway compromise, if to occur, occurs rapidly. If after brief obs period, it does not appear, it is very unlikely to be a late occurance. 

- Corrosive on GI tract. pH of detergents range from 7-9. 

- Any child with difficulty swallowing, drooling, stridor, and recurrent vomiting should have GI consulted for endoscopy

Tiki Torch Oil

- Tiki torch oil looks like apple juice (the container looks similar too)

- Lamp oil ingestion (hydrocarbons) can cause excessive drowsiness, lung injury, difficulty breathing

- Preventing accidental tiki torch oil ingestion: NEVER use torch fuels near area where food or drinks are served, keep out of reach and out of sight of young children, and only buy bottle of torch fuels with child-resistant cap and make sure to replace cap securely after every single use

Hydrogen Peroxide

- 35% hydrogen peroxide has become more popular as food-grade or nutraceutical product (food additive purportedly used for medicinal purposes)

- When hydrogen peroxide reacts with HCl in the stomach, it liberates large volumes of oxygen causing immediate frothy emesis and systemic absorption of oxygen. Gastric oxygen, once absorbed, passes through the portal vein to liver causing gas embolisms in liver

- Preferred evaluation of kids with known ingestion and acute vomiting should image by noncontrast limited upper abdominal CT (to reduce radiation exposure) to assess bubble burden. 

- There is no consensus on what is considered a significant air embolism burden that would require hyperbaric treatment

A single tablet of buprenorphine, or a single dissolvable gel strip of its formulation as Suboxone has been lethal to children.

Prescribing intranasal naloxone spray to the family of patients on buprenorphine (and methadone as well) is potentially lifesaving to the patient, should they take too much, but also for children in their homes who may accidentally eat a single tablet or chew on what appears to be a “gummy” product, a dissolvable formulation of Suboxone.

Pediatricians doing anticipatory safety guidance to parents at the 9-month-old to 1-year-old health supervision visit should ask about opiates and medication-assisted therapy present in the home or used by caregivers (especially grandparents) and should offer to write a prescription for naloxone nasal spray 

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It's back to school season which means back to school injuries! 

Scalp lacerations often require suturing or staple closure, but what if you can close the wound without any sharps that scare the kiddos? Consider using the Hair Apposition Technique (HAT)!

What is HAT?

- A very quick and easy technique for superficial scalp laceration closure made by twisting hair on each side of the laceration and sealing the twist with a small dot of glue for primary closure. 

When do I consider HAT?

- For linear, superficial lacerations that are <10cm in length 

- Laceration has achieved adequate hemostasis

- Patient has hair on both sides of the laceration

What are contraindications to HAT? 

- Hair strands are less than 3cm in length

- Laceration is longer than 10cm in length

- Active bleeding from laceration despite hair apposition

- Significant wound tension

- Laceration is highly contaminated

How do I perform HAT?

- Debride wound as you normally wound for any laceration  

- Take approximately 5 strands of hair on one side of the laceration and twist them together to make one twisted bundle

- Take approximately 5 strands of hair directly on the other side of the laceration and twist them together to make another twisted bundle

- Then take each bundle and intertwine the two bundles until the wound edges appose. 

- Place a drop of glue on the twist

- Repeat along the length of the laceration until laceration is closed

Benefits of HAT:

- Based on a RCT from Singapore that compared suturing to HAT for superficial scalp lacerations that were <10cm, patient's were more satisfied, had less scaring, lower pain scores, shorter procedure tiems, adn less wound breakdown in the HAT group compared to the sutured group. 

- A follow up study by the same group also assessed cost-effectievness of HAT compared to suturing (by taking into account staff time, need for staple/suture removal, treatment of complications, materials, etc) and found that HAT saved $28.50 USD when compared to suturing. 

Image

Modified hair apposition of scalp wounds- UpToDate

Bottom Line:

- Consider Hair Apposition Technique (HAT) for linear, superficial scalp lacerations, especially in pediatric patients as it is much more well tolerated (can also do this in adults!)

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