HAEMOPHILLIA

Acquired hemophilia is a life-threatening bleeding disorder caused by the development of auto

antibodies directed against plasma coagulation factors, most frequently factor VII utoantibodies
against other factor proteins have also been reported . Diagnosis of acquired hemophilia can be
difficult, both because the condition is rare and because the patient does not have the usual
personal or family history of bleeding episodes, such as is seen in congenital hemophilia.
Moreover, the clinical signs and symptoms of acquired hemophilia differ from those of
hereditary hemophilia.
Treatment strategies for acquired hemophilia have 2 major objectives. During acute bleeding
episodes, effective control of bleeding manifestations is the primary objective. However, the
ultimate therapeutic goal is to eliminate the inhibitor and cure the disease.
There are three types of hemophilia namely
Hemophilia A
Hemophilia B
Hemophilia C

Hemophilia A
Hemophilia A is an X-linked, recessive disorder caused by deficiency of
functional plasma clotting factor VIII (FVIII), which may be inherited or arise
from spontaneous mutation.

Signs of hemorrhage include the following:

General: Weakness, orthostasis, tachycardia, tachypnea

Musculoskeletal (joints): Tingling, cracking, warmth, pain, stiffness, and refusal to use
joint (children)

CNS: Headache, stiff neck, vomiting, lethargy, irritability, and spinal cord syndromes

Gastrointestinal: Hematemesis, melena, frank red blood per rectum, and abdominal pain

Genitourinary: Hematuria, renal colic, and post circumcision bleeding

Other: Epistaxis, oral mucosal hemorrhage, hemoptysis, dyspnea (hematoma leading to

airway obstruction), compartment syndrome symptoms, and contusions; excessive
bleeding with routine dental procedures

Hemophilia B
Hemophilia B is an inherited, X-linked, recessive disorder resulting in
deficiency of functional plasma coagulation factor IX. Spontaneous mutation
and acquired immunologic processes can result in this disorder as well.
Hemophilia B comprises approximately 20% of hemophilia cases,
approximately 50% of whom have factor IX levels of greater than 1%. Signs of

hemorrhage is as the one above.

Pathophysiology of type A

Acquired hemophilia is a spontaneous autoimmune disorder in which patients with

previously normal hemostasis develop autoantibodies against clotting factors, most
frequently FVIII.[3] The development of autoantibodies against FVIII leads to FVIII
deficiency, which results in insufficient generation of thrombin by factor IXa and the
factor VIIIa complex through the intrinsic pathway of the coagulation cascade.
The development of factor IX (FIX) autoantibodies is less common, and the presence of
autoantibodies against other clotting factorsfactors II (FII), V (FV), VII (FVII), X
(FX), XI (FXI), and XIII (FXIII), as well as von Willebrand factor (vWF)is extremely
rare.[3, 2, 4]
The most common epitopes for autoantibody binding to FVIII appear to occur between
amino acids 454-509 and 593 in the A2 domain on the heavy chain of FVIII, between
1804 and 1819 in the A3 domain on the heavy chain, and between 2181 and 2243 in the
C2 domain on the light chain.[2, 5, 6]
Anti-C2 antibodies inhibit the binding of FVIII to phospholipids and may also interfere
with the binding of FVIII to vWF protein, whereas anti-A2 and anti-A3 antibodies
impede the binding of FVIII to activated FX and FIX of the intrinsic pathway FX
activation complex.[7]
Although both alloantibody inhibitors in patients with hereditary hemophilia and
autoantibodies in patients with acquired hemophilia appear to recognize the same

epitopes on each domain, the inactivation of FVIII resulting from these interactions
differs.[8] For example, alloantibodies totally inactivate FVIII activity according to type 1
kinetics, and this total inactivation is not dependent on the titer/concentration of
circulating antibody.
In contrast, autoantibodies typically exhibit more complex type II kinetics, undergoing an
initial rapid inactivation followed by a slower inactivation curve and resulting in some
level of residual FVIII, which can be detected in the laboratory but does not seem to

Pathophysiology of type B

Factor IX deficiency, dysfunctional factor IX, or factor IX inhibitors lead to disruption of the
normal intrinsic coagulation cascade, resulting in spontaneous hemorrhage and/or excessive
hemorrhage in response to trauma. Hemorrhage sites include joints (eg, knee, elbow), muscles,
CNS, GI system, genitourinary (GU) system, pulmonary system, and cardiovascular system.
Patients who acquired HIV, hepatitis, or other viruses suffer from maladies associated with those
infections.

Hemophilia C
These occurs as a result of severe deficiency of FACTOR XI the bleeding tendency is mild.
Unlike the bleeding tendency in type A and type B, which is clearly related to the factor level, the
bleeding risk in hemophilia C is not always influenced by the severity of the deficiency,
especially in individuals with partial deficiency. Indeed, some patients with severe deficiency do
not have a bleeding tendency, whereas some patients with mild deficiency bleed excessively.

Patient Education

Clinicians should conduct one-on-one discussions of issues with patients and family members.
Because of the substantial risk of relapse, patients should be counseled to report signs of
bleeding or bruising so that relapse can be detected as early as possible. Early recognition of
relapse may minimize the time during which patients are at risk for hemorrhage.
Although pregnancy-related inhibitors tend not to recur in subsequent pregnancies in patients
who achieve complete remission, women who experience pregnancy-related acquired hemophilia
should be counseled about the possibility of recurrence in future pregnancies.

Starting in infancy, regular dental evaluation is recommended, along with instruction regarding
proper oral hygiene, dental care, and adequate fluoridation.
Encourage the patient to engage in appropriate exercise. Advise the patient against participating
in contact and collision sports.
Patient and family education about early recognition of hemorrhage signs and symptoms is
important for instituting or increasing the intensity of replacement therapy. This treatment helps
prevent the acute and chronic complications of the disease that may vary from life-threatening
events to quality-of-lifeimpairing events.
In addition, educating patients or family members about factor replacement administration at
home has greatly enhanced the quality of life of patients with severe hemophilia.

COMPLICATIONS
Complications may be divided into hemorrhagic and non hemorrhagic categories.
Hemorrhagic complications include epitasis, GI and urologic bleeding, retroperitoneal
hematomas, compartment syndrome, prolonged postpartum bleeding, excessive posttraumatic or
postoperative bleeding, subglottic or cerebral hemorrhage, and thrombocytopenia.Adverse
thrombotic events may also occur as a result of haemostatic therapy. Hemarthroses are rare.
No hemorrhagic complications include the adverse effects of immunosuppression, such as
infection, sepsis, and neutropenia.

Hemophilia A
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Hemophilia A is a hereditary bleeding disorder caused by a lack of blood clotting factor VIII.
Without enough factor VIII, the blood cannot clot properly to stop bleeding.
Alternative names

Factor VIII deficiency

Causes

Hemophilia A is caused by an inherited X-linked recessive trait, with the defective gene located
on the X chromosome. Females have two copies of the X chromosome, so if the factor VIII gene
on one chromosome doesn't work, the gene on the other chromosome can do the job of making
enough factor VIII. Males, however, have only one X chromosome, so if the factor VIII gene on
that chromosome is defective, they will have hemophilia A. Thus, most people with hemophilia
A are male.
If a woman has a defective factor VIII gene, she is considered a carrier. This means the defective
gene can be passed down to her children. In a woman who carries the defective gene, any of her
male children will have a 50% chance of having hemophilia A, while any of her female children
will have a 50% chance of being a carrier. All female children of men with hemophilia carry the
defective gene. Genetic testing is available for concerned parents.
Risk factors for hemophilia A include:

Family history of bleeding

Being male

Rarely, adults can develop a bleeding disorder similar to hemophilia A. This may happen after
giving birth (postpartum), in people with certain autoimmune diseases such as rheumatoid
arthritis, in people with certain types of cancer (most commonly lymphomas and leukemias), and
also for unknown reasons (called "idiopathic"). Although these situations are rare, they can be
associated with serious, even life-threatening bleeding.
Symptoms

The severity of symptoms vary. Bleeding is the main symptom of the disease and sometimes,
although not always, occurs if an infant is circumcised.
Additional bleeding problems are seen when the infant starts crawling and walking.
Mild cases may go unnoticed until later in life when they occur in response to surgery or trauma.
Internal bleeding may happen anywhere, and bleeding into joints is common.
Symptoms may include:

Bleeding into joints, with associated pain and swelling

Blood in the urine or stool

Bruising

Gastrointestinal tract and urinary tract hemorrhage

Nosebleeds

Prolonged bleeding from cuts, tooth extraction, and surgery

Spontaneous bleeding

Exams and Tests

If the patient is the first person in the family to have a suspected bleeding disorder, he or she will
undergo a series of tests called a coagulation study. Once a disorder has been identified, other
family members will need less testing to diagnose the disorder.
Tests to diagnose hemophilia A include:

Low serum factor VII activity.

Normal prothrombin time.

Normal bleeding time.

Fibrinogen levels are normal.

Thromboplastin time is partially prolonged.

Treatment

Initial treatment is to replace the missing clotting factor.

The amount of factor VIII concentrates needed depends on the severity of the bleeding,
The site of the bleeding, and the size of the patient.
Mild hemophilia may be treated with desmopressin (DDAVP), which helps the body release
factor VIII that is stored within the lining of blood vessels.
To prevent a bleeding crisis, people with hemophilia and their families can be taught to give
factor VIII concentrates at home at the first signs of bleeding. People with severe forms of the
disease may need regular preventive treatment.

Depending on the severity of the disease, DDAVP or factor VIII concentrate may be given before
having dental extractions or surgery in order to prevent bleeding.
Immunization with hepatitis B vaccine is necessary because of the increased risk of exposure to
hepatitis due to frequent blood infusions.
Patients who develop an inhibitor to factor VIII may require treatment with other clotting factors
such as factor VIIa, which can help with clotting even without any factor VIII.
Support Groups

For additional resources, see hemophilia support group.

Outlook (Prognosis)

The outcome is usually good with treatment. Most people with hemophilia are able to lead
relatively normal lives.
Patients with hemophilia should establish regular care with a hematologist, especially one who is
associated with a hemophilia treatment center. The ability to have quick and easy access to
medical records documenting the patient's history of factor IX levels, factor transfusions
(including the type and amount), complications, and amount of any inhibitors can be lifesaving
in the event of an emergency situation.
Possible Complications

Chronic joint deformities may occur from bleeding into joints. This complication can be
managed by an orthopedic specialist. However, joint replacement may be needed.
Intracerebral hemorrhage is another possible complication.
Repeated transfusions may slightly raise the risk for HIV and hepatitis , however, continued
improvements in blood screening procedures makes blood products safer than ever.
When to Contact a Medical Professional

Call your health care provider if:

Symptoms of a bleeding disorder develops

A family member has been diagnosed with hemophilia A

You have hemophilia A and you plan to have children

Prevention

Genetic counseling

Prenatal intrauterine diagnosis with termination of pregnancy as an option

References

Kessler CM. Hemorrhagic disorders: coagulation factor deficiencies. In: Goldman L, Ausiello D,
eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 180.
Update Date: 3/28/2010

Updated by: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine,
Department of Medicine, University of Washington School of Medicine; James R. Mason, MD,
Oncologist, Director, Blood and Marrow Transplantation Program and Stem Cell Processing
Lab, Scripps Clinic, Torrey Pines, California. Also reviewed by David Zieve, MD, MHA,
Medical Director, A.D.A.M., Inc.
Browse the Encyclopedia

MedlinePlus Topics

Hemophilia

Treatment
1) Hemsanic acid i.v stat

It is an antifibrinolytic that competitively inhibits the activation of

plasminogen to plasmin, by binding to specific sites of both plasminogen and
plasmin, a molecule responsible for the degradation of fibrin. Fibrin is a
protein that forms the framework of blood clots. It has roughly eight times
the antifibrinolytic activity of an older analogue, -aminocaproic acid

2) Ceftiriaxone
Dru Complications

Severe complications are much more common in severe and moderate haemophiliacs.
Complications may be both directly from the disease or from its treatment:[7]

Deep internal bleeding, e.g. deep-muscle bleeding, leading to swelling,

numbness or pain of a limb.

Joint damage from haemarthrosis (haemophilic arthropathy), potentially

with severe pain, disfigurement, and even destruction of the joint and
development of debilitating arthritis.

Transfusion transmitted infection from blood transfusions that are given

as treatment.

Adverse reactions to clotting factor treatment, including the development

of an immune inhibitor which renders factor replacement less effective.

Intracranial haemorrhage is a serious medical emergency caused by the

buildup of pressure inside the skull. It can cause disorientation, nausea, loss
of consciousness, brain damage, and death.

g class: Cephalosporin.