Common Bleeding Disorders

By Author: Ibrahim Machiwala
Total Articles: 463
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Hemostasis

Primary Hemostasis:
Blood vessel contraction
Platelet Plug Formation

Secondary Hemostasis:
Activation of Clotting Cascade
Deposition & Stabilization of Fibrin

Tertiary Hemostasis:
Dissolution of Fibrin Clot
Dependent on Plasminogen Activation

Classification:
Disorders of Blood vessels
Disorders of Platelets
Disorders of Coagulation
Other disorders

Tests of Hemostasis
Non specific tests:
Bleeding.T - To test Platelet & BV function
Prothrombin.T - Extrinsic, liver, warfarin
APTT - Instrinsic
Thrombin.T - Both paths. (DIC), heparin

Specific tests:
Factor assays -
Tests of thrombosis - TT, FDP, DDA,
Platelet function studies:
Adhesion, Aggregation, Release & PG pathway tests.
Bone Marrow study

Bleeding: Clinical Features
Local - Vs - General, spontaneous . .
Hematoma / Joint Bleeds- Coag
Skin / Mucosal Bleeds - PLT
wound / surgical bleeding -
Immediate - PLT
Delayed - Coagulation

Platelet ...
... Coagulation

Platelet Disorders - Features:
Mucocutaneous bleeding
Petechiae, Purpura, Ecchymosis.
spontaneous bleeding after trauma
CNS bleeding (severe ? plt)
Prolonged bleeding time (BT)

BLEEDING TIME vs. PLATELET COUNT
VON WILLEBRAND'S DiSEASE

Most common congenital disorder
Defective or deficient vWF, that mediates platelet adhesion
Factor synthesized in ???
Function --- plt adhesion, binds factor VIII and protect it from degradation
Rarely this def can cause elevated PTT d/t low factor VIII
vWD type I (80%) (AD)
vWD type II ( a and b )
vWD type III (AR)
Pseudo vWD
S/S
Mild
Musocal
Rarely posttraumatic or surgical
Exacerbated by aspirin, relieved by preg or estr use

Lab findings:
BT usually prolonged
vWF assays, factor VIII antigen or ristocetin
Platelet aggregation studies
Usually nothing apart from being cautious using aspirin

Mx.
Mild - desmopressin 0.3ug/kg effect within 90mins Q24hrly
Severe persistent - factor VIII conc.
Humate- P 20-50U/kg
AFA as adjuvant therapy given for a week after desmo or cryo to reduce likelihood of bleeding

Coagulation disorders:
Deficiencies of Clotting factors
Onset - delayed after trauma
Deep bleeding
Into joints - Hemarthroses
Into deep tissues - Hematoma
large skin bleed - Ecchymoses

Coagulation Disorders
Laboratory findings:
Normal bleeding time & Platelet count
Prolonged prothrombin time (PT)
deficiencies of II, V, VII, X
Prolonged time (aPTT)
all factors except VII, XIII
Mixing studies - normal plasma corrects PT or aPTT

Factor VIII Deficiency:
Classic hemophilia (hemophilia A)
X-linked disorder (50% daughters carriers 50% sons hemophiliac)
antenatal dx CVS (11) Amnio (16)
Most common presentation - severe bleeding -- hemearthross (knees, elbows,ankles, hips)
Spontaneous hematomas (calf , psoas)
any site incl. Intracranial --> fatal

Hemophilia A:
Most common severe coagulation disorder throughout the world
2nd to vWD among all disorders
Deficiency of factor VIII ( females least likely to be affected, unless she hs a hemophilic father and a carrier mother)
S/s
Spontaneous hemarthroses is so classical that its almost diagnostic of the disease esp if a positive family history is also present
Seropositivity for HIV via factor VIII concentrates

Lab findings:
Abnormal aPTT - Intrinsic path.
PT,BT,vWF normal
Diagnosis - factor VIII assay

Treatment:
Factor VIII concentrate (to stop bleeding & B4 surgery)
Now heat treated (free of HIV)
Recombinant factor VIII
Amount depends on the desired level of correction
I U of Factor VIII - I ml of plasma 40U/kg to acheinve 100% levels ( usually before surgery
Distribution factor of favtor VIII is 1.5 = 60u/kg
For young adult 4000 U/kg followed by 2000 U ( 30U/kg)
Q12hrly

I/V desmopressin (mild):
Cryoprecipitate (less desirable)
Pts on desmo/cryo treat with ACA(Emicar) 4gOD x 4d

Prognosis:
VIII has improved prognosis
Limited functional ability due to joint immobility 20 to joint bleeds
Hep infection
Resistance to factor VIII

Factor IX Deficiency:
Christmas disease (Hemophilia B)
X-linked recessive disorder
Indistinguishable from classic hemophilia (F VIII)
Spontaneous hemarthrosis
Coagulation factor IX def
2/3rd quantitative defect
Reduced factor IX in blood, prolonged PTT

Management:
Factor IX concentrates
80U/kg achieve 100% levels of the factor
T1/2 is 18 hrs, in major surgeries maintain 40U/kg every18hrs
Increased risk of thrombosis with this ttx
No role of desmo

Secondary Hemostatic Disorders
Acquired coagulation disorder:
Vitamin K deficiency
- neonates - decreased intestinal
flora and dietary intake
- oral anticoagulants (coumadin)
- fat malabsorption syndromes
Required for factors II, VII, IX, X
Prolonged PT and aPTT

Combined Primary and Secondary Hemostatic Disorders (DIC):
Disseminated Intravascular Coagulation
Major pathologic processes -
obstetric complications, neoplasms, infection (sepsis), major trauma
Primary - platelet consumption
(? bleeding time, ? platelets)
Secondary - factor consumption
(? PT, aPTT)

Combined Primary and Secondary Hemostatic Disorders:
Severe Liver Disease
Primary - dysfunctional platelets and/or thrombocytopenia (? BT)
Secondary - decrease in all coagulation factors except vWF (? PT, aPTT)
Vitamin K will promote synthesis of factors II, VII, IX, X

Summary Hemostatic Disorders:

o BT Plt PT PTT
Vascular Dis - ? - - -
PLT Disorder - ? - ? - -
Factor 8/9
*Congenital - - - ?
Vit K / Liver
*Acquired - - ? -?
Combined (DIC) ? ? -? ?
Summary

Hemophilia in Pakistan:
A relatively young country, with an ancient past, Pakistan achieved independence from Britain on August 14, 1947, after its bloody partition from India.
Pakistan's health care system has crumbled: public hospitals are in appalling condition, even basic treatment unavailable for many common disorders.
Private hospitals-modern and fully equipped-foster the only available research, and provide the most advanced and comprehensive care for people with hemophilia, but are extremely expensive and beyond the reach of most.
No infrastructure currently exists to provide public and free care to people with this lifelong bleeding disorder.
Of the estimated 12,000 people with hemophilia in Pakistan, only 3,100 have been identified.
Until early 1980, hemophilia was not even known to exist within the country, and only a few patients were alive. In 1982 the first blood bank was formed.
Currently only five major cities-Karachi, Lahore, Rawalpindi-Islamabad, Peshawar Multan, Faisalabad and Quetta-now have facilities to provide plasma or cryo.
And treatment at its best in Pakistan is still primitive by Western standards. Virally inactivated high or intermediate purity factor concentrates are available only to the minority elite, who are wealthy enough to pay out of pocket. But the majority of patients, the poor, receive plasma or cryo. They most often receive inferior plasma, which is not always screened for HBV, HCV and HIV.
The results-
Inferior factor replacement,
lack of patient and physician education regarding simple techniques (application of ice or ice packs, immobilization of affected joints, use of slings), and lack of physiotherapy facilities-
have contributed to the physical disability and crippling arthropathy of people with hemophilia.
50% percent of patients suffer from chronic hemophilic arthropathy.
90% of those receiving treatment are infected with HCV.
Only a handful developed AIDS during the last 15 years because the population was spared from the epidemic that swept developed countries, but most of those infected with HIV have died.
Tragically, many with hemophilia die early from intracranial hemorrhage, infection or circumcision.
Indeed, in this Muslim country where circumcision is required, approximately one-third of patients have a family history of bleeding to death after circumcision.