PART I

 Introduction
 History
 Hemostasis
 Platelet activation
 Coagulation cascade
 Phases of coagulation
 Role of each coagulation factor
 Anti thrombolytic mechanism
 Approach to child with bleeding
disorder
 Laboratory investigations
 Classification of bleeding disorders
 Bleeding disorders are usually taken to mean coagulopathies with
reduced clotting of the blood.
 Bleeding disorders characterised by abnormal platelet function or
blood vessel walls that result in increased bleeding.
 Bleeding disorders may result from faults at many different levels in
the coagulation cascade.
 1828 - Term “haemorrhaphilia” first used.
 Later shortened to “haemophilia.”
 Hemophilia is sometimes referred to as “the royal disease,” because it affected
the royal families of England, Germany, Russia and Spain in the 19th and
20th centuries. Queen Victoria of England, who ruled from 1837-1901, is
believed to have been the carrier of Hemophilia B, or factor IX deficiency.
HEMOSTASIS: The ability of the body to control the flow of blood following
vascular injury is paramount to continued survival.

 The process of blood clotting and then the subsequent dissolution of the
clot, following repair of the injured tissue.
 It is composed of 4 major events that occur in a set order following the loss
of vascular integrity:
 Vascular constriction -limits the flow of blood to the area of injury.

 Platelet aggregation –Blood platelets clump when binding to collagen that

becomes exposed following rupture of the endothelial lining of vessels.
-Blood platelets become activated and aggregate at the site of injury .
-Upon activation, platelets releaseADP and TXA2 (which
activate additional platelets).

 Clot formation -To insure stability of the initially loose platelet plug, a
fibrin mesh (also called the clot) forms and entraps the plug.

 Fibrinolysis -The clot must be dissolved in order for normal blood flow
to resume following tissue repair. The dissolution of the clot occurs
through the action of plasmin
 Normally platelets do not adhere to intact vascular endothelium.
 Subsequent to the vascular injury, platelets adhere to collagen and vWF in
the subendothelial tissue and undergo a morphological change by
assuming irregular surface, forming numerous pseudopods thus drastically
increasing their surface area.
The formation of the platelet plug involves a series of steps:

 Platelet adhesion
 After vascular injury VWf acts as a bridge between endothelial collagen
and platelet surface receptors GpIb and promotes platelet adhesion.
 The platelet glycoprotein complex I (GP-Ib) is the principal receptor
for vWF.
 Platelet secretion
 After adhesion, degranulation from both types of granules takes place with
the release of various factors.
 Release of calcium occurs here. Calcium binds to the phospholipids that appear
secondary to the platelet activation and provides a surface for assembly of
various coagulation factors.
 Platelet aggregation:

 Thromboxane A2 produced by activated

platelets
provide stimulus for further platelet aggregation.
 TxA2 along with ADP enlarge this platelet
aggregate leading to the formation of the platelet
plug, which seals off vascular injury temporarily.
 ADP binding also causes a conformational change
in GpIIb/IIIa receptors presents on the platelet
surface causing deposition of fibrinogen.
 Thrombin generation also catalyses the conversion
of this fibrinogen to fibrin which adds to the
stability of the platelet plug and is now known as
secondary haemostasis.
 Fibrinogen (factor I): consists of three polypeptide
chains - alpha, beta and gamma.
 It is converted to fibrin (factor Ia) by
thrombin (factor IIa).
 Fibrin forms a mesh around the wound
ultimately
leading to blood clot.
 The inherited disorders caused due to mutations in
fibrinogen include: Afibrinogenemia (complete
lack of fibrinogen), Hypofibrinogenemia (reduced
levels of fibrinogen) Hyperfibrinogenemia
(dysfunctional fibrinogen).
 These individuals suffer from thromboembolism.
 The gene for factor I is located on the fourth
chromosome.
 Tissue factor (factor III) :
 It is also called as platelet tissue factor.
 It is found on the outside of blood vessels and is not exposed to
the bloodstream.
 It initiates the extrinsic pathway at the site of injury.
 It functions as a high-affinity receptor for factor VII.
 It acts as a cofactor in the factor VIIa-catalyzed activation of factor
X to FXa.
 The gene for tissue factor is located on the first chromosome.
 Factor V :
 Is also referred to as proaccelerin or labile factor.
 It is enzymatically inactive and acts as a cofactor to the serine protease
FXa, which in the presence of calcium ions and an appropriate
phospholipid (PL) membrane surface enhances the activation of
prothrombin to thrombin.
 Factor V Leiden mutation causes factor V deficiency or parahemophilia,
which is
a rare bleeding disorder.
 It may also lead to myocardial infarction and deep vein thrombosis.
 The gene for factor V is located on the first chromosome (1q21-q25).
 Factor VII:
 Vitamin K-dependent serine protease.
 It initiates coagulation by activating factors IX and X simultaneously with
tissue factor in the extrinsic pathway.
 Its deficiency may lead to epitaxis, menorrhagia, hematomas,
hemarthrosis, digestive tract or cerebral haemorhages.
 The gene for factor VII is located on the thirteenth chromosome (13q34-
qter).
 Factor VIII:
 Is also known as anti-hemophilic factor (AHF).
 It is a cofactor in the activation of factor X to FXa, which is catalyzed by
factor IXa in the presence of calcium and phospholipids.
 Mutations in the factor VIII gene results in Hemophilia A. It is also
called classical hemophilia, an X-linked recessive coagulation disorder.
 It is the most common type of hemophilia. Pateints suffer from clinical
manifestations in their early childhood; spontaneous and traumatic
bleeds continue throughout their life.
 The gene for factor VIII is located on the long arm of X chromosome
(Xq28).
Factor IX:
 Is also known as Christmas factor.
 It is a proenzyme serine protease, which in the
presence of calcium activates factor X.
 Its deficiency cause Hemophilia B or Christmas
disease.
 Although, the clinical symptoms of hemophilia A and B
are similar, hemophilia B is less severe than
hemophilia A.
 High antigen or activity levels of factor IX is
associated with an increased risk of thromboembolism.
 The gene for factor IX is located on the X chromosome
(Xq27.1-q27.2).
Factor X:
 Is also known as Stuart-Prower factor.
 In the presence of calcium and phospholipid, it
functions in both intrinsic and extrinsic pathway of
blood coagulation.
 Factor X is activated to FXa by factors IX and VII. It is the
first member of the common pathway of blood
coagulation.
 FXa cleaves prothrombin to thrombin.
 Its deficiency may cause bleeding diathesis
and hemorrhages.
 Patients commonly suffer from epitaxis, gastrointestinal
bleeds and hemarthrosis. Women with factor X deficiency
may be susceptible to miscarriages.
 The gene for factor X is located on the thirteenth
chromosome (13q32-qter).
Factor XI :
 Is also known as plasma thromboplastin antecedent.
 It is a serine protease zymogen which is activated to factor XIa
by factor XIIa.
 Deficiency in factor XI causes injury-related bleeding.
 The disorder is sometimes referred to as Hemophilia C.
 Individuals with severe deficiency do not show excessive
bleeding conditions and hemorrhage normally occurs
after trauma or surgery.
 Female patients may experience menorrhagia and prolonged
bleeding after childbirth.
 The gene for factor XI is located on the distal end on the
long arm of fourth chromosome (4q35).
Factor XII :
 Is a plasma protein, also known as Hageman factor.
 It is the zymogen form of factor XIIa, which
activates factor XI and prekallikrein.
 Its deficiency does not cause excessive
hemorrhage due to lack of involvement of factor
XIIa in thrombin formation.
 However, it may increase the risk of thrombosis,
due to inadequate activation of the fibrinolytic
pathway.
 The gene for factor XII is located on the tip of
the long arm of the fifth chromosome (5q33-
qter).
Factor XIII or fibrin stabilizing factor:

 It is the proenzyme form of plasma transglutaminase.

 It is activated by thrombin into factor XIIIa in presence
of calcium.
 It forms ε-(γ-glutamyl)-lysyl bonds between the
fibrin chains and stabilizes the blood clot.
 Thus, it reduces the sensitivity of the clot to
degradation by
proteases.
 Genetic defects in the factor XIII gene leads to
lifelong bleeding diathesis.
 Patients may also suffer from intercranial bleeding and
death.
 The gene for F13A is located on the sixth chromosome
(6p24-25). The F13B gene is located on the long arm of
first chromosome (1q32-32.1)
 Von Willebrand factor (VWF):
 Is a multimeric glycoprotein involved in hemostasis.
 It supports binding of platelets to the site of injury by forming a
bridge between collagen matrix and platelet-surface receptor
complex.
 Hereditary or acquired defects of vWF lead to von Willebrand disease.
 Patients may suffer from bleeding diathesis, menorrhagia and
gastrointestinal bleeding.
 The gene for vWF is located on short arm of the twelfth chromosome
 It is therefore important that the endothelial
surface provides several proteins and receptors
that inhibit thrombin and counteract the
progress of coagulation.
 The potent thrombin inhibitor antithrombin III
binds to specific heparan sulfates of
proteoglycans in the glycocalyx that covers
the endothelial surface .
 Inadequate antithrombin III activity is
accompanied by severe thrombotic complications.
 Furthermore, a triad of endothelial receptors is
involved in the generation the important anti-
coagulant activated protein C (aPC), which can
interrupt the coagulation cascade by cleavage
of factors Va and VIIIa
The history should determine:
 The site or sites of bleeding, the severity and
duration of hemorrhage, and the age at onset.
 Was the bleeding spontaneous, or did it occur
after trauma?
 Was there a previous personal or family
history of similar problems?
 If a child or adolescent has had surgery that
affects the mucosal surfaces, such as a
tonsillectomy or major dental extractions, the
absence of bleeding usually rules out a
hereditary bleeding disorder
PHYSICAL EXAMINATION

 The P/E should focus on whether bleeding symptoms are associated primarily
with the mucous membranes or skin (mucocutaneous bleeding) or with the
muscles and joints(deep bleeding).
 The examination should determine the presence of petechiae, ecchymoses,
hematomas, hemarthroses, or mucous membrane bleeding.
 Patients with defects in platelet-blood vessel wall interaction (VWD or
platelet function defects) usually have mucocutaneous bleeding.
 Individuals with a clotting factor deficiency of factor VIII or IX (hemophilia A
or B) have symptoms of deep bleeding into muscles and joints.
 Individuals with disorders of the collagen matrix and vessel wall may have
loose joints and lax skin associated with easy bruising (Ehlers-Danlos
syndrome).
 Blood count and film
 show the number and morphology of platelets and any blood disorder
such as leukaemia or lymphoma.
 The normal range for the platelet count is 150- 400 × 109/L

 Bleeding time
 measures platelet plug formation in vivo
 normally between 3 and 10 minutes
 Prolonged bleeding times are found in patients with platelet
function defects
 Prolonged bleeding times are found in patients with platelet function
defects.
 Performed using blood collected into citrate, which neutralizes
calcium ions and prevents clotting.
 The prothrombin time (PT)
 The partial thromboplastin time (PTT)
 The thrombin time (TT)
 Correction tests
 Factor assays
 Special tests of coagulation
 Coagulation tests

 Theprothrombin time (PT)

 Time needed for the plasma to clot in the presence of tissue

thromboplastin and calcium

 Evaluates the ability of blood to clot properly

 Normal time for clotting is 10-14s

 Prolong PT results from def of:

Factor V
Factor VII
Factor X
Prothrombin
Fibrinogen
Coagulation factor deficiencies:

 Congenital
 Hemophilia A and B
 Von Willebrand’s disease
 Other factor deficiencies (rare)

 Acquired
 Liver disease
 Vitamin K deficiency, warfarin use
 Disseminated intravascular coagulation
Platelet disorders:

Quantitative disorder (thrombocytopenia)

 Immune-mediated
 Idiopathic
 Drug-induced
 Collagen vascular disease
 Sarcoidosis
 Non-immune-mediated
 Disseminated intravascular coagulation
 Microangiopathic hemolytic anemia
 Leukaemia
 Myelofibrosis
Qualitative disorder

 Glanzmann thrombasthenia
 Liver disease
 Alcoholism
Vascular disorders
 Scurvy
 Purpura
 Hereditary hemorrhagic telangiectasia
 Cushing syndrome
 Ehlers-Danlos syndrome

Fibrinolytic defects

 Streptokinase therapy
 Disseminated intravascular coagulation
Coagulation factor deficiencies
 Hemophilia A is due to a deficiency of clotting factor VIII or antihemophilic
factor or Hemophilia B is due to deficiency of clotting factor IX (hemophilia
B).
 Inherited X-link disorder
 Prevelance 1 in 5000 in male population.
 Clinical features

 Atypical profuse bleeding at circumcision

 Bruising at neonatal vaccines
 Joints and soft tissue bleeds and excessive bleeding when they
start to be active
 Prolonged bleeding after teeth extraction
 Recurrent painful hemarthrosis
 Muscle haemoatomas
 Spontaneous haematouria
 GIT hemorrhage
 Spontaneous intracranial hemorrhage (rare)
 Clinical features

 The clinical severity depend on the level of factor VIII:C = severity

of condition
 Severe = factor level < 1%
 Moderate = factor level 1 – 5%
 Mild = factor level > 5 %
 Severe disease – factor level < 1%
 Frequent spontaneous bleeding from early life

 Haemarthroses are common and may lead to joint deformity

 Bleeding into muscles is also common

 Moderate disease – factor level 1 – 5 %

 Post traumatic Bleeding

 Occasional apparently spontaneous episodes

 Mild disease – factor level > 5 %

 Usually with bleeding only after injury or surgery

 Diagnosis in this group is often delayed until quite late in

life
 Laboratory finding – investigations

 Coagulation testing
 Prolonged activated partial thromboplastin time

(APTT)
 Normal prothrombin time (PT)

 Normal bleeding time (BT)

 Factor assay (reduced level of factor VIII)

 Also known as Christmas disease

 Caused by a deficiency of factor IX

 The inheritance and clinical features are identical to

hemophilia A

 Only can be distinguished by specific coagulation factor assays

 The incidence is only about 1 in 30 000 males

 Hemophilia B is treated with factor IX concentrates

 General Management

1. Factor replacement

Bleeding is treated by administration of factor VIII concentrate by intravenous infusion.

 Minor bleeding: the factor VIII:C level should be raised to 20-30%

 Severe bleeding: the factor VIII:C should be raised to at least 50%
 Major surgery: the factor VIII:C should be raised to 100% preoperatively and
maintained above 50% until healing has occurred.

The following formulas were applied for calculating the factor dose:

Dosage (units) = body weight (kg) × desired factor VIII rise (IU/dL or % of
normal) × 0.5
Dosage (units) = body weight (kg) × desired factor IX rise (IU/dL or % of
normal)x 0.5
2. Synthetic vasopressin (Desmopressin)

 An analogue of vasopressin
 Intravenous, subcutaneous or intranasal

 Produces a rise in factor VIII:C in mild hemophilia

 It avoids the complications associated with blood

products
 It is ineffective in severe haemophilia
3.Tranexamic acid is a synthetic derivative of lysine, available for topical
and systemic usage. However, nausea is a common adverse effect.

4.The anti-fibrinolytic agent Epsilon amino caprioic acid (EACA) given

orally of IV is a potent inhibitor of initial clot dissolution. A regimen of 50
mg/kg body weight EACA given orally as a 25% oral rinse every six
hours for seven to ten days appears adequate as an adjunct.

Still tranexamic acid is 10 times more potent than EACA with fewer side-
effects.
 Hereditary coagulation abnormality caused by either:
 Reduced level of vWF
 Abnormality in vWF

Due to Point mutation or Major deletion

Vwf is a protein plays two role in action:
 It promote adhesion of platelets to the endothelium
 It is a carrier molecule for factor VIII, protecting it from premature
destruction

So in Vwd :
 Defective platelet function
 Factor VIII:C deficiency
CLASSIFICATION OF VWD:

3 TYPES:
 TYPE I:
 Characterized by a mild reduction in VWF
 usually inherited as an autosomal dominant.
 TYPE II:
 Loss of high-molecular-weight multimers, and it too is usually inherited as an
autosomal dominant
 TYPEIII:
 Characterized by severe reduction in VWF and usually inherited as
autosomal recessive.
 Clinical features

 Typically there is mucus membrane bleeding (epistaxis, menorrhage...)

 The severity of symptoms are variable with types
 Type 1, 2 usually mild symptoms

 Type 3 severe symptoms

 Laboratory Investigations:

 The bleeding time is prolonged

 APTT is prolonged
 Factor VIII is low
 VWF is usually low (type 1,2)
 Platelets count is normal
Treatment

 Depends on the severity of the condition.

 May be similar to that of mild haemophilia, including the use
of Desmopressin where possible.
 Factor VIII or Von Willebrand factor concentrates should be used to
treat bleeding or to cover surgery in patients who require replacement
therapy.
 Factor XI deficiency
 Rare
 Seen mainly in Ashkenazi Jews
 Caused bleeding only after trauma
 Treated by factor XI

 Factor XII deficiency

 Usually cause no bleeding
 Acquired coagulation disorders
 More common than inherited disorders
 Usually multiple clotting factors
 Includes
 Vitamin K deficiency

 Liver disease

 Coagulation disorders caused by antibodies

 Massive transfusion syndrome

Vitamin K is a fat soluble vitamin

 Obtained from green vegetables and bacterial synthesis in the gut

 Important on coagulation factors II, VII, IX and X and on proteins C
and S.
 Without it, these factors cannot bind calcium.
 Hemorrhagic disease of the newborn
 Biliary obstruction
 Malabsorption of vitamin K
 Vitamin K antagonist drugs
Overview of…
Biochemically the term vitamin k refers to all those compounds
that have the common naphthoquinone ring structure bellow:
Overview of…
Based on the alkyl-(R) group vitamin k may be classified as:
 vitamin K1 (Phllyoquinone) --- R-phytyl
 vitamin K2 (menaquinone)--- R-prenyl

 vitamin K3 (menadione)—no side chain

Vitamin K1 (Phylloquinone)
One of the natural forms of vitamin k found in plant sources (Green
leafy vegetables such as cabbage, spinach, cauliflower are highly
rich in vitamin k)
Animal sources (liver) are intermediate and cereals low in having vitamin
k.
Vitamin k1 is used to fortify foods and as a medication an the united
states.
Vitamin K2 (menaquinone)
Menaquinone is produced by intestinal bacteria and also present in
animal origin foods like:
Meat especially liver
Cheese
Menaquinone is used pharmacologically in some countries.
Synthetic forms of vitamin K
Vitamin k also has two synthetic forms known as:
Menadiol or Menadione
Menadiol diacetate
These two synthetic forms are converted to menaquinone
in the liver.
Both synthetic forms are water soluble and are for treatment of
VKD.
 Absorption and metabolism

Water soluble vitamin absorb directly into portal blood.

Absorbed from intestine via lymph
Fat soluble vitam(insires bile salts for absorption)

Temporarily stored in liver

Metabolized by side chain cleavage

(glucuronide conjugation )

Metabolites are excreted in bile & urine

Physiologic Functions
Vitamin k is a necessary factor for blood coagulation because it plays
role is as a cofactor in the synthesis of clotting factors II, VII, IX, X.
It is necessary for Synthesis of anti-coagulation Proteins C,S,.
Also necessary for formation of protein Z.
Mechanism of Action
Vitamin k deficiency, Etiology
At Birth or first 1-14 days of life 2-12 weeks of life Beyond infancy
24hours of life
a) Maternal intake of a) Poor transport a) Breast-feeding a) Fat- malabsorption
medications like: across the placenta b) Malabsorption Syn b) Prolonged use of
anti- TB(rifimpine,I b) No intestinal (C.F, Biliary broad- spectrum
NH), Anti- synthesis of vit-k2 obstruction) Abx.
convulsants(ph c) Inadequate c) Chronic use of c) TPN without vit-k
enobarbital, intake broad- spectrum supplementati on.
phenytoin), vitamin k d) No post-natal Abx d) Lack of oral
antagonists(wa prophylaxis d) Diarrhea, intake.
rfarin), some e) Breast-fed Hepatitis
cephalosporin' s. newborns
(delayed
feeding)
Vitamin k deficiency…
Fat malabsorption can cause vitamin k deficiency at any, these
syndromes include:
Cholestatic liver diseases (biliary atresia, alpha-1 antitrypsin
deficiency.
Pancreatic diseases
Intestinal disorders (celiac sprue, IBD, short-Bowel Syn)
C.F if liver diseases and pancreatic insufficiency was present.
Vitamin k deficiency…
Prolonged diarrhea can cause vitamin k deficiency especially in
breast-fed infants.
Its enough for a patient to receive at least for 10 days a broad-
spectrum anti-biotic to cause vitamin k deficiency in that patient.
(kaplan Med)
Clinical Manifestations of VKD
VKD causes a systemic bleeding disorder in newborn infants, the
Vitamin k-deficiency bleeding (VKDB) of the newborn.
Mild vitamin k deficiency can affect long-term bone and vascular
health.
Clinical Manifestations of VKD
Intracranial bleeding can cause convulsion, permanent
sequelae or death.
In some cases of VKD the presence of the underlying cause can be
suggested in the form of Jaundice or Failure to thrive.
Older child with VKD can present with bruising, mucocutaneous
bleeding or a more serious bleeding.
LAB Findings of VKD
Abnormal findings Normal findings
Prothrombin time(PT) BT, fibrinogen, platelets, factor5 and 8,
Partial thromboplastin time(PTT)
Decreased levels of: II, VII, IX, X
LAB Findings of VKD…
Factor VII has the shortest half-life and is the first to be affected
by VKD.
In case of Mild VKD the PT is normal but there are elevated levels
of uncarboxylated proteins known as the Proteins induced by
vitamin k absence (PIVKA).
Measurement of PIVKA- II can detect mild VKD.
Measuring of blood vit-k is less useful because of significant variations
based on dietary intake and blood levels do not always reflect tissue stores
of vitamin K.
Diagnosis of VKD
Dx of VKD is established by the presence of prolonged PT that corrects
rapidly after administration of vitamin K, which stops active bleeding.
Differential diagnosis of VKD
Other possible causes of bleeding and prolonged PT include:
DIC
Liver failure
Hereditary deficiency of clotting factors.
Vitamin C deficiency.
Differential diagnosis of VKD…
In DIC mostly due to Sepsis there is consumption of coagulation
factors and Lab investigations shows thrombocytopenia, low
fibrinogen and elevated D- dimers.
DIC is characterized by asphyxia, hypoxia, acidosis, shock and
hemangiomas and infection.
Treatment is to correct the primary clinical problem such as
infection and interrupt consumption of clotting factors and their
replacement.
Differential diagnosis of VKD…
In case of severe liver disorders like cirrhosis the production of
clotting factors is decreased and administration of vitamin k is not
effective (PT may not correct with vitamin k).
Children with hereditary disorders have deficiency of specific
factors.
Anticoagulants effects on vit-K
Warfarin and cumarin derivatives inhibit the action of vitamin k by
preventing its recycling to an active form after it functions as a cofactor
for gamma-glutamyl carboxylase.
Bleeding can occur with over dosage of warfarin and ingestion of rodent
poison (rat poison) that contains a coumarin derivate
High doses of salisylate also inhibit regeneration of vitamin k and
can cause prolongation of PT and clinical bleeding.
Anticoagulants effects on vit-K..
Warfarin prevents coagulation only in vivo and cannot prevent
coagulation of blood in vitro.
When warfarin is given to patient 2-3days are required to see its full
anti-coagulant activity and so to prevent formation of thrombosis in
these 3days we must heparinize the patient ,behind this there are two
issues:
Warfarin only acts in the liver to inhibit synthesis of the next generation of
the clotting factors, so to run out the already formed active clotting factors
from blood we must heparinize the patient.
Treatment of VKD
Acute VKDB is treated with 1mg/kg of parenteral vitamin k(0.5-
1.0mg/kg) in newborns.
After administration of vitamin k
PT should decrease within 6hours and normalize within 24hours.
Older children with acute bleeding should receive 2.5-10mg
vitamin k IM or IV.
In addition to vitamin k a Patient with severe and life- threatening
bleeding should receive infusion of fresh- frozen plasma to correct
the coagulapathy rapidly.
Treatment of VKD…
In case of malabsorption chronic administration of high doses of
oral vitamin k(2.5mg twice/wk to 5mg/day) along with bile salts
is required.
To reserve warfarin effects 25-50mg IV vitamin k1 (phytonadione
which acts rapidly) is given.
If severe bleeding occurs 10mg IM followed by 5mg 4hourly is given
with this bleeding stops in 6-12hrs but PT became normal in 24 hrs.
Prevention of VKD
IM Administration of 1mg vitamin k soon after birth prevents early
VKDB.
Discontinuing the offending medication before delivery can prevent
VKDB if this was not possible administration of 5-10mg IM vitamin k
4-12 hrs before delivery to mother may be helpful, in addition the
neonate should receive IM injection of vitamin k immediately after birth
and in severe cases use fresh- frozen plasma.
In malabsorption chronic supplementation of vitamin k and periodic
measurement of PT is necessary.
Toxicity and adverse effects of vitamin k

Fat-soluble vitamin has very low order of toxicity.

Water-soluble, synthetic vitamin k3 causes:
Vomiting
Porphyrinuria
Albuminuria
Hemolytic anemia
Hemoglubinuria
hyperbilirubinemia
Toxicity and adverse effects of vitamin k

Rapid IV injection of emulsified vit K causes:

Flushing
Breathlessness
Chest constriction
Fall in B.P
Anaphylactic reaction
Hematomas at the site of IM injection.
Association between parenteral use of vitamin k at birth and later
development of malignancy is not confirmed.
Vitamin K is also used for
Anticoagulant drug overdose
Reduces excessive menstrual blood flow
Protection against osteoporosis
Prolonged treatment with broad-spectrum ABx antibiotics
especially in ICU patients.
Obstructive jaundice, liver cirrhosis, viral hepatitis.
Prolonged high doses salisylate therapy .