Title: Bleeding disorders in childhood
1Bleeding disorders in childhood
Monika Csóka M.D., PhD 2nd Dept. of Pediatrics
2Bleeding disorder
-
- Bleeding disorders is a general term for a wide
range of medical problems that lead to poor blood
clotting and continuous bleeding. -
- Tendency to bleed longer or regularly with or
without injury.
3Hemostasis
- Cessation of blood loss from a damaged vessel.
4Coagulation
- blood vessels
- platelets
- coagulation factors
5Disturbances of hemostasis
- vasculopathy
- platelet disorders
- coagulation disorders
6Testing of coagulation
- history (family, medication, circumstances)
- phisical examination (type of bleeding)
- laboratory tests
7Testing of coagulation
8Testing of coagulation
9Laboratory tests
10Vasculopathy
- Prolonged bleeding time
- Normal platelet count and aggregation
- Vascular fragility test (Rumpel-Leed test)
11Schönlein-Henoch purpura
- Vasculitis (small arterial vessels)
- non thrombocytopenic haemorrhagic syndrome
- origin unknown (postinfectious?)
- Circulating immune komplexes (IgA, C3)
12Schönlein-Henoch purpura
- immunkomplex deposits in the skin, joints, GI
tract, kidney - Skin rash associated with arthritis and cramping
abdominal pain - Treatment anti-inflammatory drug, corticosteroid
13Thrombocytopathy
- Dysfunctional platelets
- Tendency to bleeding
- Inherited (rare) or acquired
14Thrombocytopathy
- Bleeding petechia, epistaxis, menorrhagia,
mucosal bleeding, moderate bleeding after surgery - PLT count norm., moderate decreased
- Bleeding time prolonged
15Thrombocytopathia
- Bernard-Soulier sy.
- Glanzmann thrombasthaenia
- Wiskott-Aldrich sy.
- Abnormalities of thrombocyta granules
16Bernard-Soulier syndrome
- Deficiency of platelet glycoprotein protein Ib
- Decreased ristocetin aggregation
- Thr count decreased
- Large platelets
17Glanzmann thrombasthenia
- Deficiency of GP IIb/IIIa komplex
- Type I complete absence
- Type II some complex is retained
- Platelets fail to aggregate
- Thr count normal
Both Glanzmann's thrombasthenia and
Bernard-Soulier disease respond to platelet
transfusion but this should be reserved for
severe problems as alloantibodies may form.
18Wiskott-Aldrich syndrome
- X-linked recessive disease (WASP gene codes for
the protein by the same name, which is mainly
expressed in hematopoietic cells) - Thrombocytopenia
- Eczma
- Immune deficiency
- Therapy hematopoietic stem cell transplant
(allogeneic) - supportiv care
-
19Granule deficiency
- denz granule deficiency
- Storage pool disease
- Chediak-Higashi sy.
- alfa granule deficiency
- Gray Platelet Syndrome
20Platelet dysfunction
- Drug induced
- aspirin
- indomethacin
- non-steroid antiinflammatory drugs
21Thrombocytopenia
- Autoimmune (ITP)
- Alloimmune (neonatal)
- Non-immun
- (HUS, TTP, DIC, Kassabach-Merritt sy.)
22ITP
Dendroica petechia
- Acute or chronic
- Bleeding on skin or mucosa
- Virus infection in anamnesis (1-3 weeks before)
- age 2-4 y
- in 90 remission within 6 months
- associated with other autoimmune disorder (Evans
sy.)
23ITP laboratory tests
- blood count, smear
- Antibodies against thrombocyte surface antigens
- Bone marrow aspiration
24ITP therapy
- Goal to avoid life threatening bleeding
- mild close observation
- severe IVIG or corticosteroid
- azathioprin, CP, rituximab
- Splenectomy (vaccination, penicillin)
-
- Thrombocyte concentrates only in life threatening
bleeding!!!
25ITP
- Dentistry gt 10 G/l
- Tooth extraction gt 30 G/l
- Minor surgery gt 50 G/l
- Major surgery gt 80 G/l
26TTP/HUS
- TTP
- thrombotic microangiopathy combining
microangiopathic haemolysis and thrombocytopenia
causing arteriolar occlusion by microaggregates
of platelets
27TTP/HUS
microangiopathic hemolytic anemia acute renal
failure thrombocytopenia
28TTP/HUS
- lt 5 year
- After bloody diarrhea
- E. coli (verotoxin O157H7)
- Shigella disenteriae (shiga toxin)
- idiopathic, familial
- Prodromal phase diarrhea
- 7-10 days later acute renal failure
29TTP/HUS
- Therapy fluid-electrolite
- Blood pressure
- Dialysis
30Coagulopathy
31Coagulation
- coagulation (fibrin)
- intrinsic way (plasma)
- extrinsic way (tissue)
- fibrinolisis
- control systems
32PLASMA-PHASE
33Coagulopathy 1.
- PTT U
- PT Ú
- haemophilia
- vWD
- circulating anticoagulant
- heparin
34Coagulopathy 2.
- PTT Ú
- PT U
- Factor VII deficiency
35Coagulopthy 3.
- PTT U
- PT U
- TT U
- afibrinogenaemia
- dysfibrinogenaemia
- DIC
- liver inssufficience
- heparin
36Coagulopathy 4.
- PTT U
- PT U
- TT Ú
- liver disorder
- vitamin K deficiency
- Warfarin
- Factor II, V, X deficiency
- early DIC
- dysprothrombinaemia
- ciculating anticoagulants
37Coagulopathy
- inherited
- VIII, vWf, IX, XI
- fibrinogen, II, V, VII, X, XII, XIII, combination
- acquired
- K vit., DIC, liver, heart, kidney, inhibitors
- neonatal
- haemorrhage, inherited, acquired
38Haemophilia (Greek word)
- Hereditary genetic disorder, that impair the
body's ability to control blood clotting or
coagulation. - John Conrad Otto american medical doctor
described a disease in 1803 with prolonged
clotting time
39Haemophilia
- The earliest possible implicit reference to
hemophilia may have been in the Talmud7, a
Jewish holy text, which states that males did not
have to be circumcised if two brothers had
already died from the procedure.
40Haemophilia
- The Jewish physician Moses Maimonides (1135-1204)
applied this ruling to the sons of a woman who
had married twice, thus apparently appreciating
the hereditary nature of the condition.
41Haemophilia
- In 1000 CE, the Arab physician, Abu al-Qasim
al-Zahrawi (known as Albucasis in the West),
wrote the first explicit description of
hemophilia in his Al-Tasrif, in which he wrote of
an Andalusian family whose males died of bleeding
after minor injuries.
42Haemophilia
- "the royal disease"
- Queen Victoria passed the mutation to her son
Leopold and, through several of her daughters, to
various royals across the continent, including
the royal families of Spain, Germany, and Russia.
Two of her daughters, Aliz and Beatrix were
carriers her son, Leopold had hemophilia.
43(No Transcript)
44Haemophilia
- Tsarevich Alexei Nikolaevich, son of Nicholas
II, was a descendant of Queen Victoria and
suffered from hemophilia. It was claimed that
Rasputin was successful at treating the Tsarevich
Alexei of Russia's hemophilia. Rasputin could
bring visible and significant improvement to the
condition of Alexei.
45Haemophilia
- Second common inherited coagulopathy. Prevalence
13-18/100 000 male - 1 instance in every 10,000 births for hemophilia
A and 1 in 50,000 births for hemophilia B. About
18,000 people in the United States have
hemophilia. Hemophilia usually occurs in males
and less often in females. It is estimated that
about 838 Hungarian have hemophilia A and about
192 Hungarian have hemophilia B (data from 2007).
46Haemophilia
- Haemophilia A - 90 of cases
- Haemophilia B - Christmasdisease
- Haemophilia C Factor XI deficiency
- Haemophilia AÂ Haemophilia B 41
47Clinical picture
- ecchymosis, haematom
- Deep tissue bleeding (muscle, joint)
48Clinical picture
- Umbilical cord bleeding
- Túlzott véraláfutások, belso vérzés általában a
6-9. hónapban jelentkezik, amikor a járni tanuló
gyermek elesik. Haemarthros, és intramuscularis
haematoma. - Nyomásos neuropathia, ha a vérzés idegek
közelében van. (Pl. m. iliopsoas vérzése járhat a
nervus femoralis kompressziójával). - Központi idegrendszeri vérzés
- Húgyúti vérzés, mely hasi fájdalommal és
haematuriával jár. - A bélfalba töro vérzés bélelzáródást okozhat.
49Haemophilia A
- 110.000 (80-85)
- XR
- FVIII C
- PTT U
- PT Ú
- Bleeding time, PLT Ú
50Haemophilia A
Carrier mother
Hemophilic father
Carrier mother and hemophilic father
Healthy male
Healthy female
Carrier
Hemophilic male
Hemophilic female
51Haemophilia A
- lt1 severe
- 1-5 intermediate
- gt5 mild
52 Clinical signs
- at birth or in neonate
- childhhod
53Therapy
- factor substitution
- FFP
- Cryoprecipitate
- FVIII concentrate from plasma
- recombinant FVIII
- rehabilitation
- surgery
54Complications
- Infection
- HIV
- Hepatitis (B, A, E, non A, non B, C, parvovirus)
- haemarthrosis
- hematoma
55Complications
- pseudotumor
- mucosal bleeding
- dentistry
- hematuria
- neurology
- CNS
- Spinal cord
- Periferal nerves
56Haemophilia B (Christmas)
- 150.000
- XR
- FIX
- Bleeding time, PTT U
- PT Ú/U
57Haemophilia B
- klassification, clinical picture as in
haemophilia A - Dg. later, not in neonates
- in carrier women factor level lower (25-40)
58Von Willebrand disease
- The condition first aroused his interest in the
case of a 5-year-old girl from Ã…land with an
extensive history of bleeding in her family. - Mapping her family history, von Willebrand found
23 of the girl's 66 family members were affected,
and that the disease was more common in women.
Erik Adolf von Willebrand
59Von Willebrand disease
New type bleeding disorder, different from
haemophilia 1. Mucosal bleeding (menorrhagia,
metrorrhagia, epistaxis, GI) 2. Male and female
in the same family bleed (autosomal
inheritance) 3. Bleeding time prolonged
60Von Willebrand disease
Type 1 (60-80) quantitative deficiency of vWF
(de valamennyi multimer jelen van) Type 2
(15-30) qualitative deficiency of vWF Type 3
(1-5) lack of vWF
61Von Willebrand disease
- most common hereditary coagulation abnormality
(110000) - the vWF gene is located on chromosome twelve
(12p13.2). It has 52 exons spanning 178kbp - Types 1 and 2 are inherited as autosomal dominant
traits and type 3 is inherited as autosomal
recessive. Occasionally type 2 also inherits
recessively.
62Von Willebrand disease
- Physiological function
- Endothel-platelet binding
- Binding and stabilisation of ciculating FVIII
63von Willebrand disease
- inherited
- acquired (collagen vasc. disease, Wilms tu.)
64von Willebrand disease
- LABORATORY PARAMETERS
- Screening APTI
- thr
- bleeding time
- RIPA
- Repeated examinations!
65von Willebrand disease
- LABORATORY PARAMETERS
- Special tests vWFAg
- vWFRCo
- FVIIIC
- multimer analysis (SDS elektroforesis)
- collagen-binding aktivity
- PFA-100
- Repeated tests!
66Therapy
- no regular treatment
- combined oral contraceptive pill
- human derived medium purity factor VIII
concentrates complexed to WF(antihemophilic
factor, more commonly known as Hemate-P) - Mild cases of vWD can be trialled on desmopressin
(1-desamino-8-D-arginine vasopressin, DDAVP)
67Vitamin K deficiency
- vitamin K dependent coagulation factors
- II (prothrombin)
- VII
- IX
- X
68Vitamin K deficiency
- Primer
- neonatal haemorrhagia (early, late)
- parenteral feeding, antibiotic treatment
- Malabsorption
- biliary atresia
- intestinal disease (CF)
- medicaments
- kumarin, phenytoin, salicylat
69Vitamin K deficiency
- clinic
- acute bleeding
- lab
- PTT U
- PT U
- TT Ú
70Consumptive coagulopathy
- association with other diseases
- disturbed coagulation and fibrinolysis
- acute/subacute/chronic
71Consumptive coagulopathy
- DIC
- diffuse intravascular thrombosis
- local thrombosis
72DIC
- Infection (bact., parasita, fungal, Rickettsia)
- RDS
- Asphyxia
- tumor
- Purpura fulminans
- Snake-bite
- Trauma/burn
- Haemolytic complication after transfusion
73Local thrombosis
- big haemangioma (Kasabach-Merritt sy.)
- Aorta thrombosis in neonate
- Extended venous thrombosis
- Snake-bite
74DIC -diagnosis
- Clinical signs Laboratory tests together
75DIC - therapy
- Blood transfusion
- FFP
- Thr-cc
- Heparin i.v.
- AT III
- EACA
76Bleeding disorder in neonate
- physiologic low level of factors
- liver immature
- Vitamin K deficiency
77Summary
- Coagulation is complicated, well controlled
system. We must learn much more about it.
78THANK YOU FOR THE ATTENTION!