Content: 1-Hemophilia Disorders 2-Von Willebrand Disorder 3- Complications of Plasma Factors Transfusion 4-Case scenarios

1. HAEMATOLOGICAL DISORDERS

2. Hemophilia Disorders

3. Hemophilia Disorders
■ The commonest severe inherited coagulation disorders.
■ X-linked recessive.
■ Types:
– Hemophilia A (factor 8 deficiency), occurs in 1 in 5000 males
– Hemophilia B (factor 9 deficiency), occurs in approximately 1 in
25,000.
■ The lack of factor 8 or factor 9 delays the generation of
thrombin, which is crucial to forming a normal, functional
fibrin clot and solidifying the platelet plug that has formed in
areas of vascular injury.

4. ■ Clinical Manifestations
 The severity of the disorder is determined by the degree of clotting
factor deficiency
1. Patient with less than 1% of factor 8 or 9 (severe hemophilia)
 may have spontaneous bleeding or bleeding with minor trauma.
1. Patients with 1% to 5% of factor 8 or 9 (moderate hemophilia)
 usually require moderate trauma to induce bleeding episodes.
1. Patient with >5% of factor 8 or 9 (mild hemophilia)
 significant trauma is necessary to induce bleeding; spontaneous
bleeding does not occur.

5. ■ Almost 40% of cases present in the neonatal period, particularly
with intracranial haemorrhage, bleeding post-circumcision or
prolonged oozing from heel stick.
■ Most children present towards the end of the first year of life,
when they start to crawl or walk (and fall over). Bleeding episodes
are most frequent in joints and muscles. (hemarthroses)
■ The hallmark of severe disease is recurrent spontaneous
bleeding into joints and muscles, which can lead to crippling
arthritis if not properly treated. (figure 22.16)
■ Mild hemophilia may go undiagnosed for many years

6. ■ Laboratory Studies.
– Platelet count: (normal)
– PT: (normal)
– aPTT: (prolonged)
A normal platelet count, normal PT, and a prolonged aPTT are characteristic
of hemophilia A and hemophilia B
– Specific factor assay
■ To measure the level of deficiency and confirm the diagnosis

7. Management
■ Recombinant concentrate for FVIII OR FIX
– given by prompt intravenous infusion whenever there is
any bleeding.
■ (DDAVP):
– Desmopressin acetate is a synthetic vasopressin analog
with minimal vasopressor effect. Desmopressin triples or
quadruples the initial factor 8 level of a patient with mild or
moderate(not severe) hemophilia A, but has no effect on
factor 9 levels.
■ Prophylaxis
– given to all children with severe haemophilia A (intravenous
via a central line every 2–3 days); help prevents chronic
joint disease. by raising the baseline level above 2%.

8. ■ Recommended links:
– https://www.youtube.com/watch?v=nkC1vZaUpxs
– https://www.youtube.com/watch?v=kKOCEIhHlb0
■ References:

9. Von Willebrand disease

10. Von-Willebrand Factor
■ Von Willebrand factor (vWF) is an adhesive protein that has two major
roles:
– adheres to subendothelial matrix, and platelets then adhere to
this and become activated
– It acts as the carrier protein for FVIII:C, protecting it from
inactivation and clearance

11. Von Willebrand Disease
■ Von Willebrand disease (vWD):
– Most common hereditary bleeding disorder (1% of population)
– Usually autosomal dominant, rarely autosomal recessive
– Females are more affected
– Results from either a quantitative or qualitative deficiency of von
Willebrand factor (vWF). This causes defective platelet plug
formation and, since vWF is a carrier protein for FVIII:C, patients
with vWD also are deficient in FVIII:C

12. ■ Classification:
– Quantitative deficient
o (partial = type 1) –
• The commonest subtype, (60–80%),
• Usually fairly mild
• often not diagnosed until puberty or adulthood.
o (absolute = type 3)
– Qualitative abnormal
o (type 2 = dysproteinemia)

13. ■ Clinical presentation
o Epistaxis
o Gingival bleeding
o Easy bruising
o Menorrhagia (heavy menstrual bleeding)
 In severe disease, factor 8 deficiency may be profound, and the patient
may also have manifestations similar to hemophilia A (hemarthrosis)

14. ■ Laboratory diagnosis;
– PTT bleeding time
 Increased
– Quantitative assay for vWF antigen (vWF:Ag)
– Qualitative assay for vWF activity (ristocetin cofactor activity)
 uses the antibiotic ristocetin to induce vWF to bind to platelets.
– Von Willebrand Factor Multimers –
 This test measures the different parts of the VWF protein. This
can help determine which type of VWD patient has.
– Factor VIII level

15. ■ Manegment:
– The treatment of von Willebrand disease depends on the severity
of bleeding.
 Desmopressin is the treatment of choice for most bleeding episodes
in patients with type 1 disease and some patients with type 2
disease.
 When high levels of vWF are needed but cannot be achieved
satisfactorily with desmopressin, vWF-containing concentrate
(Humate P) may be appropriate.

16. ■ Recommended links:
– https://www.youtube.com/watch?v=1DHyTEtRgtk
■ References:

17. Complicationsof plasma
factorstransfusion

18. ■ Complicationsof plasmafactorstransfusion:
– Allergic reactions:
 mild (urticaria): occur in 1% of patients;
 severe and anaphylactic: occur with a frequency of less than 1
case per 100,000 transfusions.
– Transfusion-related acute lung injury (TRALI) :
 non-cardiogenic pulmonary edema developing within 4–6 hours
of the transfusion of FFP.
– Febrile reactions:
 unexpected temperature rise during or shortly after transfusion.
Occasionally the fever is accompanied Chills, rigors, increased
respiratory rate, change in blood pressure, anxiety and a
headache.

19. – Citrate toxicity:
■ Citrate is the anticoagulant used in blood products. It is usually
rapidly metabolised by the liver. Rapid administration of large
quantities of stored blood may cause hypocalcaemia and
hypomagnesaemia when citrate binds calcium and magnesium.
This can result in myocardial depression or coagulopathy.
Patients most at risk are those with liver dysfunction or neonates
with immature liver function having rapid large volume
transfusion.
– Transmission of infections
– Circulatory overload:
■ This can occur, particularly in patients with renal or
cardiorespiratory failure.
– Inhibitors against deficient proteins:
■ These can develop after the transfusion of plasma in patients
with severe deficiencies of clotting factors.

20. References:
https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC2689068/
https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC3356109/

21. Cases

22. Case scenario 1Case scenario 1
■ A 5 years old boy presented to ED with massive epistaxsis
and petichial rash. He had an upper respiratory tract infection
2 weeks prior to this complain
■ Most likely diagnosis?

23. Idiopathic Thrombocytopenic Purpura
(ITP)

24. Case scenario 2Case scenario 2
■ An 8 years old girl sustained severe bleeding following tooth
extraction. She gave history of difficulty to stop bleeding after
cut wound last year
■ Most appropriate diagnosis?

25. Von Willebrand Disease
(vWD)

26. Case scenario 3Case scenario 3
■ A 2 years old boy had massive knee swelling following
trauma. He was found to have swollen right knee with limited
movement. There was no h/o fever. There is positive history
of bleeding following mild trauma. His brother died at age of
1month after massive bleeding followed circumcision
■ Most suitable diagnosis?

27. Hemophilia