Bleeding Disorders Flashcards
1
Q
What are the 2 clotting D/O we need to know?
A
Hemophilia A (Factor 8 Def)
Hemophilian B (Factor 9 Def)
2
Q
Hemophilia A is what factor deficiency?
A
8
3
Q
Hemophilia B is what deficiency?
A
Factor B
4
Q
What are the 4 types of platelet disorders?
A
- dysfunction (acquired or congenital)
- splenic sequestration
- increased destruction
- impaired production
5
Q
What are the 3 signs of bleeding disorders on physical exam?
A
- Petechiae <2mm
- Purpura 2-10 mm
- Ecchymosis >1cm
6
Q
What is petechiae?
A
focal areas of subcutaneous bleeding
DO NOT BLANCHE with pressure
may occur in periorbital areas after vomiting/coughing
7
Q
What is purpura?
A
palpable or nonpalpable
8
Q
What 5 lab studies should you order for a pt with suspected bleeding disorder?
A
CBC (platelet count)
Peripheral smear
PT/INR, aPTT
bleeding time
fibrinogen
9
Q
What does the platelet count look at?
A
# of platelets (thrombocytes) per cubic ml of blood
looks at quantity, not quality.
10
Q
What is the normal platelet count?
A
150,000-400,000
11
Q
What lab value is considered thrombocytopenia?
A
<100,000
12
Q
What can happen if the platelet count is <40,000?
A
prolonged bleeding from vascular injury can occur
13
Q
What can happen if platelet count is <20,000?
A
spontaneous bleeding
14
Q
What does bleeding time measure?
A
measures time for hemostasis (stopping of blood flow)
screens for microvasculature and platelet function
15
Q
Prolonged bleeding time occurs in what 2 disorders?
A
platelet disorders (von wildebrand’s disease)
severe thrombocytopenia
16
Q
What is the 1st hemostatis response when vessel injury occurs?
A
spastic contraction of the damaged microvessels (vasoconstriction)
17
Q
What is the 2nd hemostatic response when vessel injury occurs?
A
platelets adhere to the affected area (platelet plug formation)
18
Q
What is the 3rd hemostatic response when vessel injury occurs?
A
initiation of coagulation cascade
19
Q
Vasoconstriction is also known as what
A
vascular spasm
20
Q
Vasoconstriction
A
happens immediately
smooth muscle on damaged vessels will constrict which reduced blood flow to the area (limits blood loss)
Collagen is exposed which promotes platelets to adhere to the injury site.
21
Q
Primary hemostasis in platelet plug formation
A
platelets clump together through platelet adhesion: adhere to damaged endothelium, form platelet plug & degranulate (thromboregulation)
22
Q
what is platelet plug formation activated by?
A
glycoprotein: vWF
23
Q
What do platelets release once they adhere to exposed collagen?
A
ADP & TAz (thromboxane) to activate more platelets and increase the effect of vasoconstrictionq
24
Q
Seconday Hemostasis
A
once platelet plug has been formed, clotting factors are activated = “coagulation cascade”
Leads to formation of fibrin (from inative fibrinogen) = fibrin mesh produced all around platelet plug to hold it in place.
25
Secondary Hemostasis is comprised of what **3 pathways**?
**intrinsic** pathway
**extrinsic** pathway
**common** pathway
26
PT (prothrombin time) is prolonged with abnormalities in which pathway?
prolonged with abnormalities in **extrinsic** pathway (or common)
27
PT is used to monitor what?
warfarin (coumadin) therapy
28
What does PT assess?
liver function/damage
29
PTT or aPTT is prolonged in what abnormality?
intrinsic pathway abnormalities
30
PTT is used to monitor what?
unfractionated hepatin therapy
31
What conditions will you see an abnormal PTT with?
hemophilia
vW disease
liver damage
Vit K deficiency
32
**T/F:** INR is a more accurate reflection of PT
True
33
What is INR?
standardized ratio of prothrombin time compared to a control
results are independent of reagents or methods used
34
What is the Goal INR level dependent on?
underlying need for anticoagulation
35
What is INR used to monitor?
warfarin anticoag therapy
36
Characteristics of clotting disorders?
associated with **excessive or repetitive bleeding** at **unusual sites _(joints, muscles, GI, GU tract)_** with **normal activity**.
37
clotting disorders are classified as either ________ or \_\_\_\_\_\_\_\_\_.
clotting disorders are classified as either **_congenital_** or **_acquired_**.
38
What are the 2 **congenital clotting disorders**?
Hemophllia A & B
39
What is christmas disease?
Hemophilia B (Factor 9)
40
Which hemophilia is most common?
Hemophilia A (Factor 8 deficiency)
41
Both are **X-linked recessive**
**predominately affects males**
can affect females born to affected father and carrier mother
What dz?
Hemophilia A & B
42
Dz severity correlates with factor levels
Which dz?
Hemophilias
43
Clinical Px of Hemophilia A & B
most = asx for first few months of life
**1st episode of sx bleeding:** occurs **after newborn period** but **within 1st 2 years of life** _(spontaneous or with minimal injury)_
severe pain in weight-bearing joints **(hemophilic arthropathy)**
**Repeated episodes of bleeding**
44
MC sites of bleeding in Hemophilia
**Joints**
**muscles**
**skin**
**GI, GU**
**spontaneous hemarthrosis** = sign of severe dz
45
Lab studies for Hem A
platelet count: nml
PT: nml
**aPTT: prolonged (can be normal in prolonged disease)**
Factor 8 assay
46
Hem A mgmt
Factor 8 concentrate administration/infusions
Desmopressin (DDAVP)
47
Pt education for Hem A
**avoid trauma, high risk activity**
**avoid certain meds (ASA)**
genetic counseling
48
Potential causes of low platelets
**recent infection**
**platelet consumption syndrome**
immune d/o
**chronic liver dz**
bleeding
49
potential causes of high platelets
cause of significant **inflammation**
significant **infection**
**abnormal peripheral smear**
essential thrombocytosis sx
**iron deficiency anemia**
inappropriate clotting or bleeding
**metastatic malignancy**
50
is acquired or congenital a more common cause of platelet dysfunction?
acquired: **drugs, uremia, alcoholism, myeloproliferative disease**
51
What will lab studies show for dysfunctional platelets?
normal count and morphology
## Footnote
**prolonged bleeding time**
52
mgmt for dysfunctional platelet disorders
**discontinue offending agent**
**hemodialysis** in uremic cases
**platelet TF** if serious bleeding
53
What causes sequestering platelet disorders?
splenomegaly/hypersplenism = thrombocytopenia
post-splenectomy = ractive (thrombocytosis)
54
Increased platelet destruction disorder **(autoimmune)**
ITP (idiopathic thrombocytopenic purpura)
55
increased platelet consumption disorders
**TTP** (thrombotic thrombocytopenic purpura)
**HUS** (hemolytic-uremic syndrome)
**DIC** (disseminated intravascular coagulation)
56
Pathophys of ITP
reduced platelet llifespan due to antibody mediated destruction of platelets
57
What are the 2 types of ITP?
**Primary:** due to autoimmune mechanisms leading to **platelet destruction and platelet underproduction** that is **not triggered by an associated condition.**
**Secondary:** associated with another condition: HIV, Hep C, SLE, CLL
58
What type of ITP?
self limited
**common in children (2-4 yrs old)**
**IgG** associated
prior **viral URI**
Acute ITP
59
What type of ITP?
## Footnote
**females \> males**
**peak incidence 20-50 y/old**
**insidious onset**
**associated with other autoimmune dz, HIV**
Chronic ITP
60
CPx of ITP
can be asx
**peteichiae**
**pupura**
**hemorragic bullae** on skin & mucus membranes
**SAH, ICH**
**_splenomegaly should NOT be present_**
61
Lab studies for ITP
thombocytopenia: **Plt \<20**
Coag studies = nml
**BM: increased megakaryocytes**
Dx of exclusion
62
ITP Mgmt
**avoid platelet antagonists (NSAIDs, ASA)**
_Acute ITP:_ **resolves spontaneously,** may require steroids/splenectomy
_Chronic ITP:_ **high-dose prednisone or dexamethasone, IVIG**, _If refractory:_ splenectomy, danazol
63
Emergency ITP tx
stop bleeding
platelet TF
64
**Life-threatening complication of exposure to heparin**
results from an **autoantibody directed against endogenous platelet factor 4 (PF4)** in complex with heparin.
What dz?
Heparin-induced thrombocytopenia (HIT)
65
**Removal of IgG-coated platelets by macrophages** of the reticuloendothelial system (eg, spleen, liver, bone marrow)
What dz?
HIT
66
what is HIT associated with?
arterial and venous thrombosis (hypercoagulable)
67
tx for HIT
STOP HEPARIN
68
etiology of TTP
**Idiopathic**
Infection/autoimmune/malignancy: Includes **HIV**
Drugs
Pregnancy/post-partum
Stem-cell transplant
**Shigatoxin producing E. Coli** – follows bloody diarrhea prodrome
69
TTP CPx
**abrupt onset:** can be acute, chronic, relapsing
**fever, toxic-appearing**
**fatigue**
abdominal patin (pancreatitis common)
**HA, AMS, focal neuro deficits** (waxes and wanes)
**Skin pallor, petechiae, purpura, jaundice**
**20-50 year olds**
70
Endothelial layer of **small vessels** is damaged and results in **fibrin deposition and platelet aggregation** (platelet consumption)
As RBCs travel through damaged vessels, they are **fragmented** which results in **intravascular hemolysis.**
Pathophys of what dz?
Microangiopathic hemolytic anemia + thrombocytopenia
71
**Children with atecedent E Coli infection**
**MHA**(microangiopathic hemolytic anemia + thrombocytopenia)
Mainly seen in i**nfants and chlidren (MC follows E coli infection)**
**W/o neurologic findings**
Which dz?
HUS (Hemolytic Uremic syndrome)
72
Cpx of HUS
**Abdominal pain & bloody diarrhea** 5-10 days prior to onset
Like TTP (anemia, thrombocytopenia, fatigue), but **CNS involvement is less common**
If **neuro symptoms** predominate: **TTP**
If **renal failure** predominates : **HUS**
73
How do you differentiate between TTP and HUS?
**TTP:** neuro sx predominate
**HUS:** renal failure predominates
74
Most commonly **adults**
**Microangiopathic hemolytic anemia**
Thrombocytopenia
Renal dysfunction
**Severe CNS symptoms**
**Fever**
TTP or HUS?
TTP
75
**Mostly children**
Microangiopathic hemolytic anemia
Thrombocytopenia
**Acute renal failure**
**No CNS symptoms**
**TTP or HUS?**
HUS
76
Lab studies for **TTP-HUS**
**Microangiopathic hemolytic anemia:**
**Reticulocytosis**
**Increased LDH, indirect bilirubin**
**Negative coombs test**
Thrombocytopenia
**Schistocytes (helmet cells) on peripheral smear**
_Normal coagulation tests (separates TTP from DIC)_
**renal insufficiency**
77
**TTP-HUS** Management (adults)
**Corticosteroids**
Plasmapheresis
Rituximab for refractory cases
High-risk mortality
78
TTP-HUS mgmt in children
IVF, electrolyte repletion
79
Potentially l**ife threatening condition** in which **proteins which control blood clotting become overactive.**
Pathophys of what dz?
DIC
80
First, you get **extensive thrombosis.**
Then as clotting factors and platelets are used up, **bleeding/hemorrhage may occur.**
Widespread **platelet consumption.**
Patho of which dz?
DIC
81
What dz is typically associated with severe underlying systemic illness?
DIC
82
Widespread **activation of the coagulation cascade**--\>**increased fibrin clots** which entrap platelets--\>microthrombi cause **RBC destruction and small vessel occlusion --\>** massive **consumption of platelets, fibrin, and coagulation factors --\>** results in **uncontrolled bleeding.**
Mechanism of what dz?
DIC
83
Clinical conditions associated with which dz?
## Footnote
**•Sepsis**
* Trauma
* Cancer **(myeloproliferative disorders, solid tumors)**
* Obstetrical complications (**amniotic fluid embolus,** abruption)
* Vascular disorders (**giant hemangioma,** aortic aneurysm)
* Reactions to toxins **(snake venom, drugs, amphetamines)**
* Immunologic disorders
* Severe allergic reactions
* Hemolytic transfusion reactions
* Transplant rejection
DIC
84
DIC Clinical Px
* Variable, onset may be **acute or gradual**
* Patients **VERY sick with bleeding/clotting**: **Bleeding\>clotting**
* **Multiple organ systems affected**
* **Hemorrhage and/or thrombosis**
85
What is the origin of hemorrhage in DIC?
**microvasculature:**
- petechiae
- bleeding from venipuncture sites or surgical wounds
- GI, lung, obstetrical bleeding
86
DIC lab studies
**•Decreased platelets**
**•Increased PT & PTT**
**•Decreased fibrinogen**
•Increased fibrinolysis --\> results in increased fibrin degradation products
**•Increased D-dimer** (very sensitive): Fibrin degradation product, Assesses fibrinolysis
**•Microangiopathic hemolytic anemia** present in 25% of cases
**•Peripheral smear: schistocytes**
87
DIC Mgmt
quick recognition and aggressive tx of underlying cause
TF support:
* **Cryoprecipitate** (fibrinogen replacement)
* **FFP** (coagulation factors)
**•Platelet transfusion**
**•RBC transfusion**
88
**•Autosomal dominant** (affects males & females)
**•Most common congenital coagulopathy** (1/100)
Reduced levels of **factor VIII antigen or risocetin cofactor**
What dz?
Von Willebrand's Dz
89
Causes of acquired vW dz
MC: **bone marrow malignancies**
## Footnote
**valproic acid, SLE**
90
Von Willebrand factor serves what two main functions?
**Facilitates platelet adhesion** by linking **platelet membrane to vascular subendothelium**
Serves as a **plasma carrier for Factor VIII**
91
what is the result of low level of vWF or defect?
bleeding
92
Cpx of vW Dz
* **Bleeding** (nasal, sinus, vaginal, GI)
* **Spontaneous hemarthrosis** and soft-tissue bleed less common than in hemophilia A
* **Bleeding worse with ASA, decreases with estrogen/pregnancy**
93
vW Dz Labs
**•Prolonged bleeding time**: Helps differentiate vW disease from hemophilia: Bleeding time is normal in hemophilia
**•Low vWF (fancy confirmatory test)**: must test at different times
**•INR normal**
94
vW Dz mgmt
**•Desmopressin acetate (DDAVP) for Type 1**: Releases stored vWF from endothelial cells
**•Factor VIII infusion**
**•Humate-P**: Derived from human plasma & Contains both factor VIII and vWF
95
