Clin Med - Clinical Approach to Bleeding Patient Flashcards
What constitutes a referral to hematologist?
In a generally healthy patient:
- unusual, spontaneous ,prolonged or delayed bleeding
- abnormal coag test results obtained as part of preop eval
Ill patient w/ underlying medical issue
What is the significance of the age of onset in bleeding disorders?
- early age onset correlates w/ severity and indicates it’s congenital
- bleeding later in life may indicate an aquired problem or suggestive of milder congenital disease
Normal bruising in kids
- bruising over forehead, knees and shins appears when children begin to crawl
- small bruises over bony prominences common in preschool/school aged children
Abnormal bruising in kids
- in non-mobile (<9 mo) infant, significant bruising is unusual
- abnormal sites for bruising: back, buttocks, arms and shoulder
Good predictors of bleeding disorders
- family members diagnosed
- profuse bleeding w/ small wounds
- profuse surgical related bleeding
- muscle/joint- related bleeding
Fair predictors of bleeding disorder
- bruising
- epistaxis
- menorrhagia
- post-partum hemorrhage
Poor predictors of bleeding disorder
- family member that bruises easily
- gum bleeds
- hematuria
- BRBPR
What are important things to find out in a PMH about bleeding disorders?
- response to trauma (surgery, injury, dental procedures)
- rule out renal disease, malabsorption, Ehlers-Danlos
Why are women w/ bleeding disorders more likely to be diagnosed?
menstruation, therefore women w/ bleeding disorders are also more likely to be symptomatic
Most gynecological conditions present with what?
- bleeding, such as fibroids and polyps
- symptoms secondary to bleeding, such as endometriosis or ovarian cysts
menorrhagia
heavy menstrual bleeding that lasts for more than 7 days or results in the loss of more than 80mL of blood per menstrual cycle
How do you determine what constitutes blood loss more than 80mL in menstruation?
- clots greater than 1 inch in size
- low ferritin (Fe deficiency)
- changing a pad/tampon more than hourly (flooding)
Prevalence of bleeding disorders in women w/ menorrhagia across all age groups
~ 20%
How is the prevalence of bleeding disorders in women w/ menorrhagia effected in other populations?
- in adolescent pts w/ heavy periods since menarche: increases to 40%
- in women w/ idiopathic menorrhagia: increases to 50%
hemostasis
responsible for maintaining fluidity of blood in the vessels and thrombus formation upon loss of vascular integrity
What 2 things are required for normal hemostasis?
- normal number and function of platelets
- normal levels of clotting factors
If there are abnormalities in the hemostatic system what can be the result?
excessive bleeding or thrombosis
primary hemostasis
- formation of primar platelet plug
- involves platelets, blood vessel wall and vWF
Mucous membrane bleeding (epistaxis, menorrhagia, gums) points to a problem w/ what?
-primary hemostasis (platelet disorder or VWD)
What is the most common inherited bleeding disorder?
Von Willebrand Disease
-deficiency or dysfunction of VWF
Functions of vWF
- initiates platelet adhesion and mediates platelet aggregation
- transports and stabilizes factor 8
secondary hemostasis
-formation of fibrin through the coagulation cascade
What is the central event in blood coagulation?
generation of the enzyme thrombin from its precursor prothrombin
What is suggestive of problems in secondary hemostasis?
bleeding into soft tissues or joints
-e.g: deficiency of a coag factor
coagulation cascade
review flow chart
What does PT measure?
factor 7
What does aPTT measure?
- factor 8
- factor 9
- factor 11
- factor 12, HMWK, prekallikrein
if there is an increase in PT but PTT is normal what is the likely cause?
-factor 7 is the only thing that could be going wrong
What factors are associated with both PT and aPTT?
-fibrinogen
-prothrombin
-factors 5 and 10
(common pathway)
What are the 2 options for causes of prolonged PT and PTT?
-a protein/factor is missing
OR
-there is interference/inhibitor in the sample
mixing study
distinguishes between factor deficiency and factor inhibitors
examples of factor inhibitors that could cause elevated PT/PTT
- lupus anticoagulant
- specific factor inhibitor
If a mixing study corrects a prolonged PT/PTT, what was the causative source?
factory deficiency
If a mixing study does not correct a prolonged PT/aPTT, what was the causative source?
presence of inhibitor or lupus anticoagulant
Case:
elevated PT
normal platlets and aPTT
what is going on?
- factor 7 deficiency
possibilities: - Warfarin (milk vit.K deficiency)
- mild liver disease (Factor 7 is rate limiting)
What are the vit. K dependent factors?
- 2
- 7
- 9
- 10
Effect of warfarin on labs
- it is an anticoagulant
- works by interfering w/ vit. K so all vit. K dependent factors are effected
Case:
- elevated aPTT
- normal platelets and PT
- pt is bleeding
what is going on?
- factor 8, 9, 11 deficiency – hemophilia, VWD
- acquired inhibitor to above factors
Case:
- elevated aPTT
- normal platelets and PT
- pt is not bleeding
what is going on?
- factor 12, HMWK, prekallikrein deficiency
- presence of heparin or lupus anticoagulant
Case:
- elevated aPTT
- elevated PT
- normal platelets
- supra therapeutic warfarin - severe vit. K dependent factor deficiency
- severe liver disease
- factors 5, 10 thrombin deficiency
Case:
- elevated aPTT
- elevated PT
- decreased platelets
- DIC: check for fibrinogen and d-dimer
- severe liver disease (not common)
Case:
- normal aPTT
- normal PT
- normal platelets
- bleeding pt
- VWD
- platelet function disorder
- factor 13 deficiency (rare)
- collagen disorder
diagnostic approach to the bleeding patient?
- CBC w/ peripheral smear
- PT/INR and PTT - consider mixing study
- fibrinogen
- VWF testing
What are the different tests used for VWD to distinguish b/w a deficiency or disorder?
- VWF:Ag - VW factor antigen
- quantatative measure - VWF:RCoF - VS ristocetin cofactor
- functional measure - Factor 8 level - factor 8 stabilizes VWF
Most patients w/ VWD will have what results on PT and PTT?
normal
hemophilia testing results
- prolonged PTT (normal PT and fibrinogen)
- decreased factor levels (8, 9 and rarely 11)
hemostatic system in neonates is profoundly affected by what?
- gestational age
- postnatal age
coagulation factors in neonates
- most are decreased <50% adults levels
- procoagulant: vit. K dependent factors 2, 7, 9, 10
- anticoagulant: antithrombin 3, protein S and C
During a routine health supervision visit of a 3 y/o, you note several 1-1.5cm purpuric lesions located over both tibias of a previously healthy boy. There are no purpura on any other areas and no petechiae. Most appropriate initial diagnostic approach?
no lab studies
A 4 y/o is referred for eval of easy bruising. His mother has noticed multiple small hematomas over various areas, as well as large sized bruises over his torso, w/o any hx of injury. He often has nosebleeds that may last for 20-30 min. What labs would you send?
tier 1 testing:
- CBC
- PT
- aPTT
- fibrinogen
- von Willebrand testing
*if aPTT is normal but VWF ag and function are both low, diagnosis is VWD
A 6 y/o boy developed hematemesis after vomiting and undergoes upper GI scope. He subsequently developed a large gastric hematoma that had to be surgically resected. What labs would you send?
- CBC
- PT
- aPTT
- fibrinogen
- VW testing
- CBC, PT, VWF are normal. aPTT prolonged and corrects w/ mixing study. low factor 9. diagnosis?
- mild hemophilia B
Review lecture for more case studies
if you feel like punishing yourself
What is the most severe inherited bleeding disorder?
hemophilia
-1/5000 males; all ethnic groups
inheritance patterns of hemophilia
- X-linked recessive: 1/4 may be new mutations
- female child of affected male is obligate carrier
- male child of female carrier has 50% chance of being affected
- female child of female carrier has 50% chance of being carrier
hemophilia A is a deficiency of what factor?
-factor 8
hemophilia B is a deficiency of what factor?
-factor 9
hemophilia C is a deficiency of what factor?
-factor 11 (rare)
Although bleeding can occur at any site, the hallmark of hemophilia is what?
- deep bleeding into joints and muscles
- chronic arthropathy is major morbidity in severe patients
mild hemophilia
- factor level 6-50%
- typically presents w/ bleeding provoked by surgery or trauma
moderate hemophila
- factor level 2-5%
- frequently experience bleeding after minor trauma and less commonly may develop spontaneous bleeding
severe hemophilia
- factor level <1%
- often develop spontaneous musculoskeletal bleeding, life-threatening hemorrhage and excessive bleeding w/ minimal trauma
joint bleeding characteristics in hemophilia
- pain, tingling and warmth, followed by decreased ROM
- usually starts at toddler age
- ankle is particularly prone when the child is learning to stand - then knee
- severe chronic arthropathy can develop later in life
muscle bleed characteristics in hemophilia
- intramuscular bleeding occurs deep in the body of the muscle
- vague feeling of pain on motion, often difficult to palpate, circumference of limb is increased
- iliopsoas bleeding can hold significant amount of blood
life thratening hemorrhages in hemophilia
- CNS - may occur w/o significant trauma
- around airway
- exsanguination
If life threatening hemorrhage is expected in a hemophiliac, what should the tx be?
-aggressive tx w/ factor replacement BEFORE radiological eval
von willebrand disease
- inherited bleeding disorder caused by deficiency or dysfunction of von Willebrand factor
- most common inherited bleeding disorder
- effects men and women equally but women more likely to be diagnosed
discovery of VWD
- 1st described by dr. erik von willebrand in 1926
- called pseudohemophilia to describe sever mucocutaneous bleeding in a family
genetic characteristics of VWD
- autosomal dominant
- each child has 50% chance of inheriting affected gene
- variable penetrance
- type 3 and type 2N exhibit autosomal recessive
type 1 VWD
- partial quantitative defect of VWF
- most common - 70-80%
type 2 VWD
-qualitative VWF defect
type 3 VWD
- virtually complete deficiency of VWF
- autosomal recessive
clinical presentation of VWD
- excessive and prolonged mucocutaneous bleeding
- bruising, epistaxis, gum bleeding
- family hx of bleeding
- abnormal VWF testing
treatment fundamentals in mild hemophilia and most VWD
-factor replacement therapy may not be required for minor injuries
tx fundamentals in moderate hemophilia
-factor replacement therapy w/ bleeding episodes or to prevent bleeding that could occur during a procedure
tx fundamentals in severe hemophila
-factor replacement therapy is the mainstay of treatment
treatment options in hemophilia
- raising factor (8 or 9) or VWF levels with:
- DDAVP
- Blood component therapy - factor replacement
- adjunctive therapies:
- antifibrinolytic agents
- hormome therapy for manorrhagia
DDAVP
- desmopressin
- synthetic analogue of the antidiuretic hormone vasopressin
- increases plasma factor 8 and VWF elvels
candidates for treatment w/ DDAVP
- pts w/ type 1 VWD, mild hemophilia A and some platelet disorders
- indicated for menorrhagia, bleeding or minor procedures
how DDAVP is given
- IV or intranasal
- peak effect achieved w/i 30-90 minutes
- for menorrhagia, given on day 1 and 3 of period
treatment w/ antifibrinolytics - tranexemic acid
- stabilizes blood clot - helpful in almost any type of bleeding
- can be used alone in mild cases or along w/ factor replacement in severe cases
- another option is aminocaprioc acid
hormone therapy for menorrhagia in bleeding disorders
- combined hormonal contraception is superior to oral progesterone
- continuous is preferable to 21 day schedule
- higher doses often needed
- Mirena IUD
bleeding in newborns w/ hemophilia
- 44% of pts w/ hemophilia had neonatal bleeding
- sites: circumcision, intracranial, heel stick, IM inj sites
- risk of symptomatic intracranial hemorrhage in newborns w/ hemophilia is 4%
what is the major risk of delivery in infancy w/ suspected bleeding disorder?
- intracranial hemorrhage
- generally recommend c-section
in an otherwise healthy infant, the most common causes of bleeding are what?
- thrombocytopenia
- vit. K deficiency
- inherited coag defects
in a sick appearing baby, bleeding is often the result of what?
- liver injury
- DIC
neonatal thrombocytopenia
- consumption of platelets: ITP, neonatal alloimmune thrombocytopenia, hepatic hemangioma
- inadequate production: bone marrow suppression or infiltration
NAIT
- neonatal alloimmune thrombocytopenia
- placental transfer of maternal IgG antibodies against fetal platelet ags inherited from father
presentation of NAIT
- bruising, petechiae or rarely ICH - otherwise well appearing
- normal maternal platelet count
prenatal management of NAIT
- planned c-section
- avoid aspirin and NSAIDs
- tx w/ maternal IVIG
- maternal steroid
- serial intrauterine platelet transfusions
neonatal management of NAIT
- can closely monitor if plat cout is >30k and no bleeding
- if <30k:
- random platelet transfusion
- HPA-1a negative platelets
- maternal platelets
- IVIG
inhibitory systems to terminate clotting
- AT3 (antithrombin)
- APC (activated protein C/S)
- TFPI (tissue factor pathway inhibitor)
AT3 function in clot termination
- passive
- inactivates thrombin, factor 9 and 10
APC function in clot termination
- dynamic
- inactivates co-factors - 5 and 8
TFPI function in clot termination
- dynamic
- inhibits tissue factor
how does heparin work
-by potentiating the activity of AT3
