ITP +

HUS+
HAEMOPHILIA
a 22 yr girl presented to u with the history of purpuric spot
What are the causes of purpuric spot?
Ans.
 I.T.P.
 Aplastic anaemia
 Leukaemia
 DIC
 Henoch- schonlein purpura
 Dengue
 SLE/ vasculitis
Q. What type of disease it is?
Ans. Autoimmune disease.
Q. Who are mostly affected?
Ans. Female.
Q. Which antibody is formed and against whom it works?
Ans. Antibody IgG
It is against platelet membrane glycoprotein IIb, IIIa.
pathogenesis autoimmune disease
auto anti-body –against the platelet
membrane glycoprotein IIb/IIIa resulting in
premature removal from the circulation the
reticulo¬endothelial system
is it a isolated disease or in some case it may present single
associated with other disease
autoimmune disease most case are associated with
underlying immune dysregulation
such as
 connective tissue diseases,
 HIV infection,
 B cell malignancies,
 pregnancy
 drug
Q. When I.T.P is called acute and chronic?
Ans. Acute I.T.P when duration <6 weeks
Chronic I.T.P  when duration >6 weeks.
CLINICAL depends on the degree of thrombocytopenia
FEATURE if count is < 20 × Spontaneous bleeding
109/L occurs
higher than this easy bruising or
epistaxis or
Menorrhagia
No organomegaly
onset- insidious
sex —more in female
age in child-- history of a
preceding viral infection
absent in adult
over 65 years- look for B
cell malignancy
investigation The peripheral blood film is normal except
of thrombocytopenia
bone marrow reveals increase in
megakaryocytes

appropriate autoantibody testing a

diagnosis of connective tissue disease

HIV testing
 no treatment if platelet count > 30 × 109 and stable patient

increased surgery and

bleeding risk biopsy
if spontaneous 1st line therapy prednisolone 1 mg
bleeding / kg daily
slow response to IVIg with steroid
acute only steroids alone or
case treat if a severe haemostatic
failure
Persistent or platelet
potentially life- transfusion in
threatening bleeding addition to the
other therapies.
 1st Relapses re-introducing corticosteroids
two relapses, or splenectomy
primary refractory
disease,
symptom despite low-dose
splenectomy corticosteroid
immunosuppressive rituximab,
chronic
ciclosporin and
tacrolimus
if severe second-line therapy with the thrombopoietin
thrombocytopenia analogue romiplostim
with or without
significant bleeding thrombopoietin receptor
persists despite agonist eltrombopag
splenectomy
what is the mechanism of action of steroid and IVIg in ITP ?
steroid suppress antibody production and inhibit
phagocytosis of sensitised platelets by
reticuloendothelial cells
intravenous raise the platelet count by blocking
immunoglobulin antibody receptors on reticuloendothelial
(IVIg) cells
What is the role of splenectomy in ITP?
complete remission in about 70%
improvement in 20–25%,
require further medical only in 5–10% of patients
therapy
What are the differences between purpura and spider neavi?
purpura spider neavi
Due to extravasation of blood Due to arteriolar dialation
No blanch on pressure blanch on pressure
Due to ↓ platelet Due to ↑estrogen
Q. What are the characters of pupura of vasculitis?
Ans. Painful and tender & palpable
What is the cause of I.T.P. in splenectomized patient?
Ans. Probably patient has ectopic spleen.
when u start treatment in a patients without significant bleeding
symptoms
severe thrombocytopenia (<5000/μL), or signs of impending
bleeding (such as retinal hemorrhage or large oral mucosal
hemorrhages) can be instituted as an outpatient using single agents
Evans simultaneous or sequential association of autoimmune
syndrome hemolytic anemia (AIHA) with immune thrombocytopenic
purpura
Evans syndrome is a very rare autoimmune disorder in which the
immune system destroys the body's red blood cells, white blood cells
and/or platelets. Affected people often experience thrombocytopenia
(too few platelets) and Coombs' positive hemolytic anemia (premature
destruction of red blood cell)
Manifestations of Evans syndrome may include the following, in
descending order of frequency:
Thrombocytopenia
Anemia
Neutropenia
Pancytopenia
Signs of include purpura, petechiae, and
thrombocytopenia ecchymoses.
Signs of anemia include pallor, fatigue, and light-
headedness.
Jaundice may indicate hemolysis.
Splenomegaly –haemolytic anemia
Treatment Prednisone (most commonly used
first-line agent)
Intravenous immune globulin (IVIg;
for those with persistent immune
cytopenia and those who require
prolonged or high doses of steroids)
Coagulation disorders that cause a bleeding tendency
X-linked Haemophilia A and B
Congenital disorders Autosomal von Willebrand disease
Factor XI deficiency
Defiiencies of all other coagulation factors
Hypofirinogenaemia
Drug-induced Inhibition of function Heparins
Acquired disorders Fondaparinux
Rivaroxaban
Apixaban
Dabigatran
Inhibition of synthesis Warfarin
Under-production Liver failure
Increased consumption Coagulation Disseminated
activation intravascular
coagulation (DIC)
Immune-mediated Acquired haemophilia
and von Willebrand
syndrome
Others Acquired factor X defiiency (in amyloid)
Acquired von Willebrand syndrome in Wilms
tumor
A patient came to you with recurrent swelling of right knee joint
after fall, during playing. What is your diagnosis?
Ans. Haemophilia.

Q. What type of disease it is?

Ans. X- linked disease.
Q. Which factor responsible for haemophilia?
Ans. Factor VIII.
Q. Is any other factor responsible?
Ans. Factor IX, Which other name Haemophilia B or Christmas disease
Where factor VIII is synthesized?
Factor VIII is primarily synthesised by the liver and endothelial cells
What is the half life of Factor VIII?
Ans. 12 hours.
What is the function role of von Willebrand factor ?
factor VIII is bind to to von Willebrand and thus it protected from proteolysis in the
circulation
Q. Can female be affected?
Ans. Yes. Female can be affected in following conditions:
 Lyonisation theory
 If affected father marry carrier female
 Turner’s syndrome
Q. What do you mean by Lyonisation theory?
Ans. Females have 2 ’X’ chromosomes. Random inactivation of one `X’
chromosome is called Lyonisation theory.
Q. who will u do antenatal diagnosis ?
Antenatal diagnosis by chorionic villous sampling
what is the genetic of hamophilia ?
Genetics The factor VIII gene is located on the X chromosome
large deletions-- is associated with Severe haemophilia
while single-base changes--- result in moderate or mild
disease
Classification of haemophilla depending of severity?
(ISTH criteria) (ISTH = International Society on Thrombosis
and Haemostasis)
Severity of Factor VIII or IX level Clinical presentation
haemophilia
Severe < 0.01 U/mL (<1%) Spontaneous
haemarthroses and
muscle haematomas
Moderate 0.01–0.05 U/mL (1- Mild trauma or
5%) surgery causes
bleeding
Mild > 0.05 to 0.4 U/mL Major injury or
(1–40%) surgery results in
excess bleeding
clinical feature depend of severity
site of bleeding skin,
into muscle and joints,
retroperitoneal and intracranial
severe case Spontaneous large joints,
haemarthroses / joint especially knees,
swelling elbows, ankles and
hips.
muscle haematomas calf muscles
psoas muscles
Retroperitoneal and
intracranial bleeding

moderate case bleeding after Mild trauma or surgery causes

Mld case excess bleeding after Major injury or surgery

What are the complication of haemophilia ?
recurrent joint bleeding secondary osteoarthrosis
psoas haematoma femoral nerve compression
calf haematomas compartment syndrome
Shortening of the Achilles tendon.
What are the joint change occur in haemophilia ?
in acute cases a hot, swollen and very painful joint
in chronic cases or synovial hypertrophy, destruction of
Chronic haemophilic the cartilage and secondary
arthropathy osteoarthrosis and muscle wasting of
that joint
X—ray change broadening of the femoral epicondyles
or intercondyler fossa
reduced joint space
other changes of osteoarthritis
 sclerosis
 osteophyte
 bony cysts
Treatment of severe haemophilia A, IV infusion of factor VIII concentrate
haemophilia mild or moderate  DDAVP (vasopressin receptor agonist )
haemophilia A o 0.3 μg/kg IV / SC
 Intranasal 300 μg.
if develop anti-factor activated clotting factors, e.g. VIIa or FEIBA,
VIII antibodies FEIBA-- factor VIII inhibitor bypass activity
(FEIBA)
supportive resting of the bleeding site by either bed rest
or a splint
Once bleeding has settled, the patient should
be mobilized and physiotherapy used to
restore strength to the surrounding muscles
immunization against hepatitis A and B
‘prophylaxis’ or factor VIII can be administered 2 or 3 times
treatment ‘on per week as ‘prophylaxis’ to prevent
demand’ for bleeding bleeding in severe haemophilia
what is the adverse effect of DDAVP?
water retention
signifiant hyponatraemia
contraindication of DDAVP ?
patients with a history of severe arterial disease / thrombotic event

Complications of coagulation factor therapy?

serious complication of factor development of anti-factor VIII antibodies
VIII infusion Such antibodies rapidly neutralise therapeutic
infusions, making
treatment relatively ineffective
it occur in about 20% case
in that case to stop bleeding use
 Infusions of activated clotting factors, e.g. VIIa or
 factor VIII inhibitor bypass activity (FEIBA)

BLOOD BORNE DISEASE HIV

hepatitis viruses HBV and HCV
vCJD
What are the investigations you will suggest?
Ans. BT- normal, CT- prolonged. [ In ITP, BT- normal, CT-
normal] Ideally PT, APTT should be done. PT- normal,
APTT- increased.
Q. Tell something about pedigree of Haemophilia?
Ans. If father is affected → all daughters will be carrier, all
sons will be spared. If mother is carrier → 50% of
daughters will be carrier, 50% sons will be affected.
von Willebrand disease
Q. WHAT is Von-Willebrand disease?
It is an autosomal dominant coagulation disorder due to impaired
function of VonWillebrand factor.
Q. What is the source of Von-Willebrand factor?
It is produced by: Endothelial cell, platelet.
Q. What is the function of Von-Willebrand factor?
 It is a carrier protein of factor VIII. And protect the factor from
proteolysis & defiiency of vWF
lowers the plasma factor VIII level.
 It also form bridges between platelet and sub-endothelial
component.
Q. Gene of Von-Willebrand factor present in which chromosome?
Ans. Chromosome no 12
Q. Von-Willebrand factor present in which blood group?
Ans. Blood group A and B
people with blood group O have lower circulating vWF levels than
individuals with non-O groups
type of Von-willebrand disease ?
two types
a quantitative (types 1 and characterised by a quantitative
3) defiiency decrease of von Willebrand factor
(vWF),with normal functional
protein.
qualitative (type 2) defiiency vWF molecules are functionally
abnormal.
what is the genetic ?
it is AD disease
Within a single family, the disease has variable penetrance, so
that some members may have quite severe and frequent bleeds,
whereas others are relatively asymptomatic.
clinical feature  Superficial bruising,
 Epistaxis,
 Menorrhagia and
 Gastrointestinal haemorrhage
investigation  vWF and factor VIII, and
 bleeding time prolongation
 clotting time
 platelet count
 specific tests of function to determine
binding to platelet glycoprotein Ib (RIPA)
RIPA = ristocetininduced platelet
agglutination
treatment  Mild haemorrhage
o local means or
o with DDAVP,.
o Tranexamic acid may be useful in
mucosal bleeding.
 Serious or persistent bleeds
o factor VIII
Liver disease
causes of oesophageal varices
bleeding in liver peptic ulcer
disease Thrombocytopenia due to to
hypersplenism
reduced hepatic synthesis, factors V, VII,
VIII, IX, X, XI, prothrombin and fibrinogen
cholestatic jaundice-- reduced vitamin K
absorption RESULT deficiency of factors II,
VII, IX and X
When will treat acute bleeds
interventional procedures such as liver
biopsy
how will treat plasma products or
platelet transfusion
if Vitamin K deficiency parenteral vitamin K
in renal failure severity of e haemorrhagic state is
proportional to plasma urea level
causes are multifactorial
 anaemia, mild thrombocytopenia
 accumulation of low molecular weight--
inhibit platelet function
 dialysis to reduce the urea concentration
 severe or persistent bleeding
 platelet concentrate infusions and red cell
transfusions
 other Increasing the concentration of
vWF, either
o by cryoprecipitate or
o by DDAVP
The thrombotic micro-
angiopathies
The thrombotic These are a group of conditions
microangiopathies characterised by microvascular
thrombosis, microangiopathic haemolytic
anaemia and
thrombocytopenia.

Renal involvement, due to occlusion of

glomerular capillaries and renal arterioles by
platelet–fibrin thrombi,
causes Haemolytic uraemic syndrome (HUS)
Thrombotic thrombocytopenic purpura (TTP)
Disseminated intravascular coagulation (DIC)
TTP
TTP TTP has prominent microvascular neurological effects
(usually confusion) and is caused by an inherited or
acquired deficiency of the von Willebrand factor (vWF)-
cleaving metalloprotease, ADAMTS13, that normally
degrades ultra-large multimers of vWF to smaller vWF
proteins; this leads to enhanced platelet–vWF
adhesion, enhanced platelet aggregation and
microangiopathic haemolysis
Clinical C == CNS/NEUROLOGICAL sequelae
feature R== Renal impairment
A== microangiopathic haemolytic anaemia
F== Fever
T== Thrombocytopenia
HO etiology  drugs (ticlopidine, ciclosporin),
 HIV,
 shiga toxins and
 malignancy
investigation  PBF haemolytic anaemia
 reticulocyte count  ↑
 Platelet count -↓
 PT and APTTN
Treatment  Emergency plasma exchange.
 Corticosteroids,
 aspirin and
 rituximab
Haemolytic uraemic
syndrome (HUS)
Haemolytic The hemolytic uremic syndrome (HUS) is defined by
uraemic the simultaneous occurrence of microangiopathic
syndrome (HUS) hemolytic anemia, thrombocytopenia, and acute
renal injury
classified into Diarrhoeal HUS (D+ HUS) is associated with a
two major preceding diarrhoeal illness, commonly caused by
subtypes Escherichia coli HUS has prominent renal
involvement and is. O157:H7
Atypical HUS (aHUS) is associated with mutations in
proteins of the alternative pathway of complement,
particularly complement factor H
causes Associated with verotoxin-producing E. coli
Other
familial,
drugs,
cancer
investigation PBF-- anaemia with features of intravascular
haemolysis
Platelet count --↓
unconjugated bilirubin level↑
LDH↑
haptoglobin ↓& reticulocytosis
Management fluid and electrolyte balance
transfusion and RRT if necessary
Infusion of fresh frozen plasma
(act by replacing complement components)
10 mL/kg daily for seven days
Plasma exchange (presumably by removing
pathogenic autoantibodies).
anti-C5 monoclonal antibody, eculizumab, which
binds to C5, thereby preventing activation of the
terminal complement cascade.
DIC
DIC Disseminated intravascular coagulation (DIC, also called
consumption coagulopathy and defibrination syndrome) is
a systemic process producing both thrombosis and
hemorrhage
patho-physiology systemic inflammatory respond  release cytokine 
activate intrinsic pathway & release of procoagulant
substances tissue factor result in generation of
intravascular fibrin clotsresult multi-organ failure
microthrombus deposition which can result in acute
kidney injury, acute respiratory distress syndrome, skin
necrosis /purpura fulminans /gangrene, and organ failure
such as liver failure, heart failure and adrenal failure
simultaneous consumption of coagulation factor and
plateletcausing bleeding
There is consumption of platelets, coagulation factors
(notably factors V and VIII) and fibrinogen. The lysis of
fibrin clot results in production of fibrin degradation
products (FDPs), including D-dimer
DIC Ta-- Trauma ,Tissue destruction, e.g. pancreatitis, burns
causes Ta-- Toxic/immunological, e.g. ABO incompatibility, snake
bites, recreational drugs
M-- Malignancy, e.g. solid tumours and leukaemias
O--- Obstetric, e.g. amniotic fluid embolism, placental
abruption, pre-eclampsia
V--- Vascular abnormalities, e.g. vascular aneurysms, liver
haemangiomas
I --Infection/sepsis
l --- Severe liver failure
investigation CBC &PBF --anaemia
APTT --↑
PT --↑
fibrinogen--↓,
platelet count --↓
FDPs--↑
DIC  Rx underlying cause (antibiotic if sepsis)
 Correction of
o dehydration, hypoxia and
o renal failure acidosis,
 Blood component therapy,( bleeding or
high bleeding risk)
o such as fresh frozen plasma,
o cryoprecipitate and
o platelets
 Prophylactic doses of heparin
 Established thrombosis ----
o unfractionated heparin
if sepsis-
 activated protein C concentrate
Antiphospholip Antiphospholipid syndrome (APS) is a
id syndrome clinicopathological entity in which a constellation
(APS) of clinical conditions, alone or in combination, is
found in association with a persistently positive
test for an antiphospholipid antibody.
CLINICAL  Adverse pregnancy outcome
FEATURE o Recurrent first trimester abortion (≥ 3)
o Unexplained death of morphologically
normal fetus after 10 weeks' gestation
o Severe early pre-eclampsia
 Venous thromboembolism
 Arterial thromboembolism
 Livedo reticularis, catastrophic APS, transverse
myelitis, skin necrosis
CAUSES ho ateiology to remember ===BRTC(s)
 Behçet's syndrome
 Rheumatoid arthritis
 Temporal arteritis
 SLE
 Systemic sclerosis
 Sjögren's syndrome
INVESTIGATION  Anticardiolipin antibody
 lupus anticoagulant test or dilute Russell
viper venom time (DRVVT)
 APPT
Antiphospholi If stroke,…. should be treated with
pid syndrome warfarin
(APS)
If VTE ….. life time / long-term
anticoagulation after a first event
If associated with pregnancy --
heparin and aspirin