bleeding disorders , itp, dic, hus

1. Bleeding disorders
Approach to
Fatmah Ali Almohimeed
341212406

2. CONTENT
1 ITP
2 DIC
3 HUS
4 Kasabach-Merritt syndrome

3. 2 weeks after a viral syndrome, a 2 y.o. develops
bruising and generalized petechiae that is more
prominent over the legs. He has neither
hepatosplenomegaly nor lymph node enlargement.
Laboratory testing reveals a normal hemoglobin,
hematocrit, and white blood cell count and
differential. The platelet count is 15,000/mm3.
Which of the following is the most likely diagnosis?
A. Acute lymphoblastic leukemia
B. Aplastic anemia
C. ITP
D. Thrombotic thrombocytopenic purpura
E. von Willebrand disease

4. ITP: Idiopathic to Immune01
William J. Harrington -a fellow in the training program at the Barnes Hospital-
decided to study the theory that there was a factor in the blood
of patients with ITP that was destroying platelets. So, when a
patient with persisting ITP despite splenectomy was admitted to
the hospital in the summer of 1950, the perfect opportunity
greeted them. Platelet counts were tested on both the woman
patient and Harrington and started the exchange transfusion.
Shortly thereafter, Harrington sustained a major seizure. Over
the course of the next 4 days, Harrington’s platelet count
remained dangerously low and he had widespread petechia and
bruises. By the fifth day, the platelet count was nearing normal
and examination of Harrington’s bone marrow before and after
the exchange transfusion revealed no changes in the
megakaryocytes indicating an effect on the circulating platelets
and not on the megakaryocytes. Thus, the Harrington–
Hollingsworth experiment identified an immune, or rather an
autoimmune, basis for this disease changing the name from
“idiopathic” to “immune” thrombocytopenia purpura.

5. Immune Thrombocytopenic Purpura

6. EPIDEMIOLOGY :01
COMMONEST 50-65% 1-4yr
cause of
thrombocytopenia
in childhood.
Has recent history
of viral illness
Is the peak
age
1 in 20,000 more in late winter and spring
1-4 wk. after exposure to a common viral infection, an autoantibody directed
against the platelet surface cause sudden onset of thrombocytopenia.
the
=

7. PATHOGENESIS01

8. ETIOLOGY01

9. CLINICAL MANIFESTATION01
-sudden onset of generalizedpetechiae and purpura
-Epistaxis and other mucosal bleeding, rare to be profuse bleeding.
- Splenomegaly, lymphadenopathy,bone pain, and pallor are rare.

10. classification system has been proposed to characterize the severity
of bleeding in ITP on the basis of symptoms and signs :
01
31
42
No symptoms
Moderate
more severe skin and mucosal lesions,more
troublesome epistaxisand menorrhagia
Mild
bruising and petechiae,
occasional minor epistaxis,
v.little interference with daily living。
Severe
bleeding episodes:menorrhagia, epistaxis,melena -
requiring transfusionor hospitalization,symptoms
interfering seriouslywith the qualityof life

11. DDx:02
Congenital cause
(such as Wiskott–Aldrich or Bernard–Soulier syndromes)
Acquired (ALL, Aplastic anemia)
presence of anaemia, neutropenia,
hepatosplenomegaly, or marked
lymphadenopathy
Immune
Nonimmune
SLE, Alloimmune neonatal
thrombocytopenia.
Increased platelet destruction
or consumption:
HUS, TTP, DIC, CHD, Kasabach–Merritt
syndrome, Hypersplenism
Impaired platelet production:
Platelet count normal:
Platelet dysfunction
Congenital: Rare disorders, e.g. Glanzmann thrombasthenia,
Acquired: Uraemia, cardiopulmonary bypass
Vascular disorders
Congenital Rare disorders, e.g. Ehlers–Danlos, Marfan syndrome,
Acquired Meningococcal ,Vasculitis, e.g HSP

12. INVESTIGATIONS:03
thrombocytopenia(platelet count <20 × 109/L) is
common but can be lower than 150
-Platelet size may be increase
-HB , WBC , RBC are normal
-To exclude leukaemia or aplastic anaemia
- Megakariocytosis seen
CBC:
Bone marrow aspiration

13. TREATMENT01
acute benign Self-limiting*The disease is & &
(usually remittingspontaneously within 6–8 weeks)
*Most children do not need any therapy even if their platelet count is less than 10 × 109/L
The Treatment should be given if there is evidence of major bleeding (e.g. intracranialor gastrointestinal
hemorrhage) or persistent minor bleeding that affects daily lives :
Start with IVIG If inadequate response , short course of Prednisone
- thrombopoietic growth factors?Splenectomy ?platelet transfusion?

14. DIC

15. DIC02

16. DIC02
 Paradoxical condition leading to
Both clotting and bleeding
 A confusing disorder from
both diagnostic and therapeutic standpoints:
Lack of uniformity in clinical manifestation
Lack of uniformity in the laboratory diagnosis
Lack of uniformity or consensus on management
Many unrelated diseases can trigger DIC
 Any life-threatening severe systemic disease associated with
hypoxia, acidosis, tissue necrosis, shock, and/or endothelial
damage may trigger DIC.

17. PATHOGENESIS02
ANY
TRIGGER !
01 04
02 03
Activation and release of
cytokines and chemokines
alter endothelial function
more prothrombotic state
formation of
microvascular
thrombosis and
organ failure
Consumption of
anticoagulant
proteins > bleeding

18. Clinical manifestation :02
- The predominantclinicalfeature is bruising, purpura and haemorrhage.
- The pathophysiological process is characterizedby microvascularthrombosis and purpura fulminans may
occur. May lead to necrosis

19. Clinical manifestation :02

20. Investigations:02
- Prothrombin time
(PT)
- APTT
- fibrinogen
degradatio
n products
- D-dimers
- +Schistocyt
e in blood
smear
Platelet
Fibrinogen ,
factors II, V,
and VIII
proteins C and
S
Antithrombin
anticoagulants

21. treatment02
1
2
3
*
*
*
Treat the underlying cause of the DIC
(usually sepsis)
Providing intensive care.
Fresh frozen plasma (to replace clotting factors)
and platelets.
DIC

22. Hemolytic-Uremic
Syndrome

23. 03
Acute renal failure
HUS is a common cause of
community acquired acute
kidney injury in young children
HUS is most common in
preschool and school-age
children

24. ETIOLOGY02
medication genetic infection
* HUS commonly is transmitted by undercooked meat or unpasteurized milk and caused mainly by
E.coli and shigella ( verotoxin-shiga toxin ) The most common form of HUS is caused by toxin-producing E coli that causes prodromal
acute enteritis and is commonly termed diarrhea-associatedHUS. The most common toxin is O157:H7.
* HUS associated with systemic diseases characterized by microvascularinjury

25. CLINICAL MANIFESTATIONS03
* Sudden onset of pallor, irritability, weakness, and lethargy
* Oliguria
* HUS can present with either significant dehydration or volume overload
* HTN & Jaundice & petechiae

26. INVESTIGATIONS:03
*Thrombocytopenia , platelet counts usually 20,000-
100,000/mm3
*mild elevations in serum blood urea nitrogen and
creatinine
*Urinalysis typically shows microscopic hematuria and
low-grade proteinuria.
*Peripheral smear may show Schistocyte
*May need stool culture

27. INVESTIGATIONS:03

28. TREATMENT04
Supportive care
Management of fluid
and electrolytes
Control of hypertension
Dialysis if the patient
becomes significantly
oliguric or anuric.

29. A three week old white female had a history
of a hemangioma of left thigh and buttock
diagnosed at birth. MRI at six days of age
showed subcutaneous and muscle infiltration
involving the left thigh and buttock with
extension into the abdominal wall. The
patient was admitted with increased size of
the left thigh, worsened purple color of the
thigh, and severe thrombocytopenia (platelet
count = 16 x 10(9)/L).

30. Giant hemangioma
(Kasabach-Merritt syndrome)

31. Giant hemangioma
04
The associationof a giant hemangioma with localizedintravascularcoagulationcausing thrombocytopeniaand hypofibrinogenemia is
called
Kasabach-Merritt syndrome
It is a life-threatening combination of giant hemangioma, thrombocytopenia, hemolytic anemia
and consumptive coagulopathy as a result of platelet and red blood cell trapping and activation of the
clotting system within the vasculature of the hemangioma

32. Clinical manifestation :02
- cutaneous giant hemangioma and rarely located in viscera
- ecchymosis, petechiae
- Painful lesions
- Anemia

33. INVESTIGATIONS:03
-The platelet count is depressed
-Bone marrow contains increased numbers of normal or immature megakaryocytes.
-The thrombocytopenia has been attributed to sequestration or increased destruction of platelets
within the lesion.
-decreased levels of clotting factors are relatively common

34. Treatment03
SURGICALWOMAN
pharmacological
-excision of small lesions, although this is often difficult because of coagulopathy.
-Additional pharmacologic treatments include systemic steroids with or without
vincristine as first-line therapy in most cases.

35. Helpful clinical features in evaluating bleeding disorders04
Age of
onset
Bleeding
history
Pattern
of
bleeding
Family
history

36. References:03
WOMAN
- Illustrated Textbook of Pediatrics
5th Edition 2018
- Nelson Essentials of Pediatrics 8th
Edition 2019

37. THANK YOU
FOR YOUR lISTENING