Clin Med - Clinical Approach to Bleeding Patient Flashcards
(95 cards)
1
Q
What constitutes a referral to hematologist?
A
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
2
Q
What is the significance of the age of onset in bleeding disorders?
A
- 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
3
Q
Normal bruising in kids
A
- bruising over forehead, knees and shins appears when children begin to crawl
- small bruises over bony prominences common in preschool/school aged children
4
Q
Abnormal bruising in kids
A
- in non-mobile (<9 mo) infant, significant bruising is unusual
- abnormal sites for bruising: back, buttocks, arms and shoulder
5
Q
Good predictors of bleeding disorders
A
- family members diagnosed
- profuse bleeding w/ small wounds
- profuse surgical related bleeding
- muscle/joint- related bleeding
6
Q
Fair predictors of bleeding disorder
A
- bruising
- epistaxis
- menorrhagia
- post-partum hemorrhage
7
Q
Poor predictors of bleeding disorder
A
- family member that bruises easily
- gum bleeds
- hematuria
- BRBPR
8
Q
What are important things to find out in a PMH about bleeding disorders?
A
- response to trauma (surgery, injury, dental procedures)
- rule out renal disease, malabsorption, Ehlers-Danlos
9
Q
Why are women w/ bleeding disorders more likely to be diagnosed?
A
menstruation, therefore women w/ bleeding disorders are also more likely to be symptomatic
10
Q
Most gynecological conditions present with what?
A
- bleeding, such as fibroids and polyps
- symptoms secondary to bleeding, such as endometriosis or ovarian cysts
11
Q
menorrhagia
A
heavy menstrual bleeding that lasts for more than 7 days or results in the loss of more than 80mL of blood per menstrual cycle
12
Q
How do you determine what constitutes blood loss more than 80mL in menstruation?
A
- clots greater than 1 inch in size
- low ferritin (Fe deficiency)
- changing a pad/tampon more than hourly (flooding)
13
Q
Prevalence of bleeding disorders in women w/ menorrhagia across all age groups
A
~ 20%
14
Q
How is the prevalence of bleeding disorders in women w/ menorrhagia effected in other populations?
A
- in adolescent pts w/ heavy periods since menarche: increases to 40%
- in women w/ idiopathic menorrhagia: increases to 50%
15
Q
hemostasis
A
responsible for maintaining fluidity of blood in the vessels and thrombus formation upon loss of vascular integrity
16
Q
What 2 things are required for normal hemostasis?
A
- normal number and function of platelets
- normal levels of clotting factors
17
Q
If there are abnormalities in the hemostatic system what can be the result?
A
excessive bleeding or thrombosis
18
Q
primary hemostasis
A
- formation of primar platelet plug
- involves platelets, blood vessel wall and vWF
19
Q
Mucous membrane bleeding (epistaxis, menorrhagia, gums) points to a problem w/ what?
A
-primary hemostasis (platelet disorder or VWD)
20
Q
What is the most common inherited bleeding disorder?
A
Von Willebrand Disease
-deficiency or dysfunction of VWF
21
Q
Functions of vWF
A
- initiates platelet adhesion and mediates platelet aggregation
- transports and stabilizes factor 8
22
Q
secondary hemostasis
A
-formation of fibrin through the coagulation cascade
23
Q
What is the central event in blood coagulation?
A
generation of the enzyme thrombin from its precursor prothrombin
24
Q
What is suggestive of problems in secondary hemostasis?
A
bleeding into soft tissues or joints
-e.g: deficiency of a coag factor
25
coagulation cascade
review flow chart
26
What does PT measure?
factor 7
27
What does aPTT measure?
- factor 8
- factor 9
- factor 11
- factor 12, HMWK, prekallikrein
28
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
29
What factors are associated with both PT and aPTT?
-fibrinogen
-prothrombin
-factors 5 and 10
(common pathway)
30
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
31
mixing study
distinguishes between factor deficiency and factor inhibitors
32
examples of factor inhibitors that could cause elevated PT/PTT
- lupus anticoagulant
| - specific factor inhibitor
33
If a mixing study corrects a prolonged PT/PTT, what was the causative source?
factory deficiency
34
If a mixing study does not correct a prolonged PT/aPTT, what was the causative source?
presence of inhibitor or lupus anticoagulant
35
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)
36
What are the vit. K dependent factors?
- 2
- 7
- 9
- 10
37
Effect of warfarin on labs
- it is an anticoagulant
| - works by interfering w/ vit. K so all vit. K dependent factors are effected
38
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
39
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
40
Case:
- elevated aPTT
- elevated PT
- normal platelets
- supra therapeutic warfarin - severe vit. K dependent factor deficiency
- severe liver disease
- factors 5, 10 thrombin deficiency
41
Case:
- elevated aPTT
- elevated PT
- decreased platelets
- DIC: check for fibrinogen and d-dimer
| - severe liver disease (not common)
42
Case:
- normal aPTT
- normal PT
- normal platelets
- bleeding pt
- VWD
- platelet function disorder
- factor 13 deficiency (rare)
- collagen disorder
43
diagnostic approach to the bleeding patient?
- CBC w/ peripheral smear
- PT/INR and PTT - consider mixing study
- fibrinogen
- VWF testing
44
What are the different tests used for VWD to distinguish b/w a deficiency or disorder?
1. VWF:Ag - VW factor antigen
- quantatative measure
2. VWF:RCoF - VS ristocetin cofactor
- functional measure
3. Factor 8 level - factor 8 stabilizes VWF
45
Most patients w/ VWD will have what results on PT and PTT?
normal
46
hemophilia testing results
- prolonged PTT (normal PT and fibrinogen)
| - decreased factor levels (8, 9 and rarely 11)
47
hemostatic system in neonates is profoundly affected by what?
- gestational age
| - postnatal age
48
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
49
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
50
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
51
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
52
Review lecture for more case studies
if you feel like punishing yourself
53
What is the most severe inherited bleeding disorder?
hemophilia
| -1/5000 males; all ethnic groups
54
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
55
hemophilia A is a deficiency of what factor?
-factor 8
56
hemophilia B is a deficiency of what factor?
-factor 9
57
hemophilia C is a deficiency of what factor?
-factor 11 (rare)
58
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
59
mild hemophilia
- factor level 6-50%
| - typically presents w/ bleeding provoked by surgery or trauma
60
moderate hemophila
- factor level 2-5%
| - frequently experience bleeding after minor trauma and less commonly may develop spontaneous bleeding
61
severe hemophilia
- factor level <1%
- often develop spontaneous musculoskeletal bleeding, life-threatening hemorrhage and excessive bleeding w/ minimal trauma
62
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
63
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
64
life thratening hemorrhages in hemophilia
- CNS - may occur w/o significant trauma
- around airway
- exsanguination
65
If life threatening hemorrhage is expected in a hemophiliac, what should the tx be?
-aggressive tx w/ factor replacement BEFORE radiological eval
66
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
67
discovery of VWD
- 1st described by dr. erik von willebrand in 1926
| - called pseudohemophilia to describe sever mucocutaneous bleeding in a family
68
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
69
type 1 VWD
- partial quantitative defect of VWF
| - most common - 70-80%
70
type 2 VWD
-qualitative VWF defect
71
type 3 VWD
- virtually complete deficiency of VWF
| - autosomal recessive
72
clinical presentation of VWD
- excessive and prolonged mucocutaneous bleeding
- bruising, epistaxis, gum bleeding
- family hx of bleeding
- abnormal VWF testing
73
treatment fundamentals in mild hemophilia and most VWD
-factor replacement therapy may not be required for minor injuries
74
tx fundamentals in moderate hemophilia
-factor replacement therapy w/ bleeding episodes or to prevent bleeding that could occur during a procedure
75
tx fundamentals in severe hemophila
-factor replacement therapy is the mainstay of treatment
76
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
77
DDAVP
- desmopressin
- synthetic analogue of the antidiuretic hormone vasopressin
- increases plasma factor 8 and VWF elvels
78
candidates for treatment w/ DDAVP
- pts w/ type 1 VWD, mild hemophilia A and some platelet disorders
- indicated for menorrhagia, bleeding or minor procedures
79
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
80
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
81
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
82
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%
83
what is the major risk of delivery in infancy w/ suspected bleeding disorder?
- intracranial hemorrhage
| - generally recommend c-section
84
in an otherwise healthy infant, the most common causes of bleeding are what?
- thrombocytopenia
- vit. K deficiency
- inherited coag defects
85
in a sick appearing baby, bleeding is often the result of what?
- liver injury
| - DIC
86
neonatal thrombocytopenia
- consumption of platelets: ITP, neonatal alloimmune thrombocytopenia, hepatic hemangioma
- inadequate production: bone marrow suppression or infiltration
87
NAIT
- neonatal alloimmune thrombocytopenia
| - placental transfer of maternal IgG antibodies against fetal platelet ags inherited from father
88
presentation of NAIT
- bruising, petechiae or rarely ICH - otherwise well appearing
- normal maternal platelet count
89
prenatal management of NAIT
- planned c-section
- avoid aspirin and NSAIDs
- tx w/ maternal IVIG
- maternal steroid
- serial intrauterine platelet transfusions
90
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
91
inhibitory systems to terminate clotting
- AT3 (antithrombin)
- APC (activated protein C/S)
- TFPI (tissue factor pathway inhibitor)
92
AT3 function in clot termination
- passive
| - inactivates thrombin, factor 9 and 10
93
APC function in clot termination
- dynamic
| - inactivates co-factors - 5 and 8
94
TFPI function in clot termination
- dynamic
| - inhibits tissue factor
95
how does heparin work
-by potentiating the activity of AT3
