Hemorrhagic diatheses in children

1

• Hemorrhagic diatheses in children

Sakharova I. Ye., M.D, Ph.D
2
The stopping of a bleeding is carried out due to
three parts of a hemostasis

• Vascular integrity.
• Qualitative and quantative characteristics of
  platelets.
• Presence of coagulation factors in blood.

3
According to this all hemorrhagic diatheses are
divided into 3 groups 1. Vasopathies
2. Thrombopathias 3. Coagulopathies
4
Schönlein-Henoch purpura (synonims -
anaphylactoid purpura, allergic angiitis,
small-vessel vasculitis, hemorrhagic vasculitis,
Henoch-Schönlein disease) is one of the collagen
vascular diseases in which basis lays immune
complex mechanism of small vessels wall damaging
with skin, joints, intestine and kidneys
affection.
5
Clinical features.

• The skin rush urticarial initially then fades,
  to be replaced by symmetrical macular or papular-
  macular hemorrhagic purpuric lesions. They may
  remain small and discrete or enlarge and become
  quite blotchy, at times confluent. Sometimes in
  the center of blots can be necrosis.
• Typical places of rush localization extensor
  surfaces of legs, on the feet, over the joints,
  on the buttocks occasionally, they may occur on
  the hands, extensor surfaces of arms, elbows, and
  face, but very rarely on the trunk.

6
(No Transcript)
7
(No Transcript)
8
(No Transcript)
9
(No Transcript)
10
Clinical features of the Schönlein-Henoch
purpura.

• joints involvement
• acute abdominal pain, vomiting, melena
• renal involvements (microscopic hematuria, with
  or without proteinuria)
• scrotal involvement (epydidimitis, orchitis,
  and scrotal bleeding)

11
Laboratory findings

• General blood count reveals normochromic anemia,
  eosinophilia.
• Mild leukocytosis and elevated ESR, which are
  associated with inflammatory process.
• The platelet count, platelet function test, and
  bleeding time are normal.
• Blood coagulation studies are normal.
• Urinalysis frequency reveals hematuria,
  proteinuria.

12
Laboratory findings

• The ASO (antistreptolizin-O) titer is frequently
  elevated and the throat culture positive for
  group A beta-hemolytic streptococcus.
• Serum Ig A may be elevated.
• Circulating immune complexes are commonly
  present.
• Positive C-reactive protein, increased level of
  sialic acids (acute phase reactants).
• Hypercoagulation orientation of hemostasis
  parameters.

13
Basic therapy of hemorrhagic vasculitis

• Antiaggregants (disaggregants) for 3-4 weeks
• ? Kurantil (Dipiridamol) 2-4 mg/kg/day (IV, IM,
  per os)
• ? Trental 5-10 mg/kg/day (IV, per os)
• ? Tiklopedin (Tiklid) 250 mg 3 times /day
• Direct anticoagulants for 3-4 weeks (under PTT
  control)
• ? Heparin 200-300 U/kg/day (IV, SC)
• ? Fracsiparin (Calciparin, Enocsiparin) 5000-7500
  U/day (SC)

14
Basic therapy of hemorrhagic vasculitis

• Fibrinolysis activators
• - Ac. nicotinici (IV)
• Nonsteroidal antiinflammatory drugs, NSAID for
  2-3 weeks
• ? Aspirin 5-10 mg/kg 1 time in morning
• ? Indomethacin 2-4 mg/kg/day
• ? Ortofen 1-2 mg/kg/day

15
Other treatment

• Corticosteroids prednisone 3-4 mg/kg/day for 5-7
  days (corticosteroids therapy may provide
  symptomatic relief for severe gastrointestinal or
  joint manifestations, but doesnt alter skin or
  renal manifestations)
• Cytostatics (methotrexate 50 mg/m2,
  azathioprine 50-75 mg/day or cyclophosphamide
  100-150 mg/day)
• Penicillin in full therapeutic doses for 10 days
  (if culture for group A beta-hemolytic
  streptococcus is positive or if the ASO titer is
  elevated)
• Antihistamines and less sedating agents (in
  patients with urticarial lesions)
• Plasmapheresis with substitution of 2-5 plasma
  volumes

16
(No Transcript)
17

• Idiopathic thrombocytopenic purpura (ITP,
  primary immune thrombocytopenic purpura,
  autoimmune thrombocytopenic purpura)
• describes an autoimmune disorder in which the
  number of circulating platelets is less than 150
  G/l.

18
Clinical features.

• The onset of the disease is usually sudden. The
  symptoms of intoxication and fever usually are
  absent.
• Skin purpura, which arises either spontaneously
  or secondary to trauma. The type of rush is
  petechial-bruise. Petechiae may be found anywhere
  over the skin. Ecchymoses are usually found on
  the anterior surfaces of the lower extremities,
  over bony prominences such as the ribs, scapula,
  shoulders, and legs. Petechiae may be found in
  the conjunctiva, oral cavity mucose, in the soft
  palate. It is significant that rush is
  polymorphous and polychromatic.

19
(No Transcript)
20
Clinical features.

• The second frequent clinical sign are bleedings.
  In the beginning of the disease can be nose
  bleeding (epistaxis), bleeding from gums, mucous
  membranes, gastrointestinal tract, kidneys and
  metrorrhagias (uterinal bleedings). Hemorrhage
  into the central nervous system, the most serious
  complication of thrombocytopenia.

21
Laboratory findings

• A marked decrease or absence of platelets
• Prolonged bleeding time by Duke (gt 4 min)
• Poor clot retraction (normally occurs within an
  hour at 37 ºC)
• Bone marrow examination often the increased
  number of immature megacaryocytes with a markedly
  basophilic cytoplasm
• Antiplatelet antibodies are present in blood
  serum
• Abnormal tourniquet test

22
(No Transcript)
23

• Children who have platelet
  counts gt30,000/mm3 (30 x 109 /l) and are
  asymptomatic or have only minor purpura do not
  require routine treatment. Children who have
  platelet counts lt20,000/mm3 (20 x 109 /l) and
  significant mucous membrane bleeding and those
  who have platelet counts lt10,000/mm3
  (10 x 109 /l) and minor purpura should receive
  routine treatment.

24
Treatment of ITPI stage (acute heteroimmune
ITP)

• Prednisolon 1 mg/kg/day
• Dicynon 0.25 mg x 3 times/day or 12,5 1-3 ml
  Doxium, Androkson
• Vitamin C, K, calcium medicines
• Antifibrinolytic agents aminocaproic acid
  0,05-0,1 g/kg/day

25
Treatment of ITPII stage (chronic autoimmune ITP)

• Prednisolon 1 mg/kg/day
• Intravenous immune globulin (IVIG) 400 mg/kg/day
  during 2-5 days IG Biochemi Austria,
  endoglobulin, Austria sandoglobulin,
  Switzerland intraglobulin, Germany
• Anti-D(Rh) immunoglobulin (intravenous Rh immune
  globulin)
• ?2-interferon
• Plasmapheresis

26
Treatment of ITPIII stage

• Splenectomy
• IV stage
• Steroid use and immunosuppressives therapy
  According to a recent study, using a combination
  of weekly vincristine, weekly methylprednisolone,
  both until platelet counts reached 50,000/mm3,
  and cyclosporine orally twice daily until the
  platelet count is normal for 3-6 months seems
  promising, though larger prospective studies are
  needed.

27

• Wiskott-Aldrich syndrome (congenital
  thrombocytopenia) an X-linked disorder, the
  initial manifestations are often present at birth
  and consist of petechiae, bruises and bloody
  diarrhea due to thrombocytopenia.
• The classic triad of this syndrome includes
  thrombocytopenia, eczema and immunodeficiency

28

• Von Willebrand's disease (vWD) is inherited as
  an autosomal dominant disease. There is deficient
  or defective production of von Willebrand factor.
  This protein mediates platelet adhesion to the
  endothelium and protects factor VIII from
  degradation.

29

• Can be classified as
• Type I
• Type II
• Type III
• pseudo-vWD,
• based on their clinical history and laboratory
  evaluation

30
Laboratory findings

• ? The platelet count is normal
• ? Prolonged protrombin time (normal 12-15 sec.)
• ? Prolonged bleeding time by Duke (gt 4 min)
• ? Decreased ristocetin cofactor activity in
  plasma
• ? Low level of antihemophilic globulin (AHG F
  VIII)
• ? Reduced platelets adhesiveness

31
Treatment

• Depends from the type of the disease
• ? Type I - Desmopressin acetate (DDAVP), an
  analogue of vasopressin 0,3 ?g/kg IV or
  intranasal DDAVP (Stimate)
• ? Type II, III cryoprecipitate or platelet
  transfusions

32

• Bernard-Soulier syndrome is an autosomal
  recessive disorder with characteristic easy
  bruizability and severe bleeding in injury.
• Lab. Findings
• the platelet count is normal or slightly
  decreased
• bleeding time is prolonged
• platelets are very large in peripheral blood
  smear.

33

• Hemophilia A and B are inherited bleeding
  disorders caused by deficiencies of clotting
  factor VIII (F VIII - antigemophilic globulin
  (AHG)) and factor IX (F IX - plasma
  thromboplastin component (PTC) or Christmas
  factor) correspondingly.

34
Mechanism of hemophilia inheritance
35
Classification(according to the F VIII and F IX
levels)
Severety of hemophilia F VIII and F IX levels
Severe Moderate Mild Subclinical lt 1 1 5 5 15 15 50
36
Laboratory diagnostic of hemophilia

• Prolonged coagulation time
• (normal 5-10 min by Lee-White)
• Prolonged recalcification time
• (normal 80-140 sec)
• Prolonged heparin time
• (normal 11-16 min)
• Prolonged protrombin consumption (partial
  thromboplastin) time
• (normal 25-39 sec)

37

• Prophylactic treatment
• The aim of this treatment is to maintain 5
  factor activity in patients blood.
• Start from the age of 1-2 years.
• Use monoclonal-antibody purified F V??? ,
  F ?? and recombinant F V??? , F ?? 3 times in
  week in hemophilia A and 2 times in week in
  hemophilia B 25-40 IU/kg.

38
Treatment of acute bleeding episodes

• Hemophilia A
• Fresh frozen plasma (100 ml80IU ?HG) Dose is
  10-15 ml/kg IV during 30-60 min, repeat after
  8-12 hours.
• Cryoprecipitate
• Monoclonal-antibody purified F V??? and
  recombinant F V???
• Hemophilia A
• Fresh frozen plasma
• Monoclonal-antibody purified F IX and
  recombinant F IX

39

• During severe or dangerous (e.g. CNS,
  retroperitoneal) bleeds need to obtain 50-100
  factor activity for 7-10 days. For less critical
  situations (e.g. dental extractions, haematuria,
  soft tissue bleeds), 20-50 factor activity for
  2-7 days are generally sufficient. For
  uncomplicated haemarthroses or superficial muscle
  or soft tissue bleeds, 20-30 for 1-2 days.

40
Laboratory differential diagnostics of
hemorrhagic diatheses