hemost Flashcards

1
Q

which chemicals are secreted by the endothelium in a physiological state?

What is their purpose?

A

nitric oxide

PGI2: prostacyclin

>> inactivates platelets

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2
Q

which proteins are on the surface of endothelial cells having an impact on coagulation?

A
  • heparin sulfate
    • binding Antithrombin
    • >>> AT3 is inactivating circling coag factors:
    • 2,9,10
  • Thrombomodulin
    • binding Thrombin (= 2)
    • Thrombin activates Protein C
    • >>> inactivates 5,8
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3
Q

Name the 5 steps of hemostasis

A

vascular spasm

platelet plug formation

coagulation

clot retraction and repair

fibrinolysis

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4
Q

how does muscular spasm occur?

A
  • Endothelin is secreted by endothelium

if endothelium damaged and exposing underlying receptors

>> endothelin can bind and causes contraction of musc

  • Myogenic mechanism: automatic contraction if muscular layer is exposed
  • Nociceptor activation: activation of nociceptors under basal membrane stimulate muscle contraction
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5
Q

which factors do endothelial cells produce when they are injured?

which factors do they stop to make after injury?

what is the consequence?

A
    • Van Willebrand factor
    • nitric oxide and prostacycline (PGI2)
  • >>> binding of platelets to vWf
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6
Q

what do bound platelets secret?

A
  • ADP > chemtaxis plat
  • Thromboxin A2 > chemotax plat.
  • Serotonin
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7
Q

What are the binding sites on platelets?

A

GP 1b: binding to vWF

GP 2b/3a: binds to Fibrinogen and links platelets

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8
Q

Who is secreting Thromboxane A2 and what are its functions?

A

secreted by platelets that are activated by vWf binding

  • chemotaxis for other platelets
  • activates smooth muscle contraction together with serotonin
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9
Q

who produced factor XII and how is it activated?

A

liver

activted by clotting platelets and their negative surface charges

activates factor 9

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10
Q

what happens after factor 12 activation?

A

12 activates

  • 11
  • 9
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11
Q

What happens after activation of factor 9?

A

9 + Platelet Factor 3 + Calcium

activate 10

10 +PF3 + Calcium + Factor 5

>>>> Prothrombin Activator

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12
Q

factor 2 is also called

A

thrombin

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13
Q

What is the purpose of prothrombin activator?

A

activates factor II

so prothrombin >>> thrombin

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14
Q

who activates fibrinogen and what happens?

A

Thombin (2) activates soluable Fibrinogen and turn it into a clotlike structure: Fibrin

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15
Q

what is the purpose of thrombin and who is activated by?

A

activated by prothrombin activator

> activates fibrinogen -> fibrin

> activates factor 8

> factor 8 is the fibrin stabilator (cross linking)

> fibrinogen -> fibrin mash

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16
Q

What is the first step of the common pathway?

A

10

(10 + 5 + Calcium + PF3)

activates prothromin activator

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17
Q

what is the intrinsic pathway and how is it activated?

A

factor 12 activation by surface of bound together platelets

12 > 11 > 9 > 8

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18
Q

What is the extrinsic pathway

A

much faster than instrinsic

needs 30 seconds

  • factor 3 released from damaged tissue
  • activates factor 7
    • 7 can either activate 9 of the instrinsic pathway or
    • 7 can start common pathway
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19
Q

name the factors of the intrinsic pathway

A

contact factors, 12,10,9,8

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20
Q

name the factors of the extrinsic pathway

A

3,7

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21
Q

name the factors of the common pathway

A

10 + 5 > 2> 1

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22
Q

how can you test the extrinsic pathway?

when does it become abnormal?

A

PT

Prothrombin time: 16-20sec in horses!

(tests pathway except 3 - 3 is always there anyways)

so basically testing factor 7

time prolongs when there is <30% of factor 7 left

7 has the shorest half life of all factors!

also used to monitor Vit K deficiency

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23
Q

how can you test the instrinsic pathway?

A

PTT (partial thromboplastin time)

APTT (activated PTT): 45-66sec

more sensitive to environment like difficult venipuncture… can be false slower/faster/normal

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24
Q

clotting times in horses with DIC

A

usually long APTT

with normal PT

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25
which clotting factors are Vit K dependant?
2,7,9,10
26
What happens during Clot retraction and repair
1. platelet contraction 2. platelets: secretion of * **PDGF (platelet derived growth factor)** \> * helps repair connective tissue with plaques * proliferate smooth muscle * **VEGF (vascular endothelial growth factor)** * regenerate epithelial lining
27
What happens during fibrinolysis
= 5. step of coagulation cascade protein on surface of endothelial cells: **tissue plasminogen activator** binds to **plasminogen** that is present in the blood converts **plasminogen to plasmin** **PLASMIN eats FIBRIN** and thereore releases **D-DIMER and fibrinogen** into circulation
28
What does D-Dimer measurement help you with?
If there was formation of blood clots and fibrinolysis
29
what does tissue plasminogen activator do?
turns plasminogen into plasmin which will eat clot
30
what does heparin do?
**enhances Antithrombin 3** activity | (AT3 _inactivates_ **2,9,10**)
31
What does aspirin do?
inhibits Thromboxin A2 that is normally released by platelets when they bind together to attract more platelets
32
what is warfarin?
Vitamin K oxide reductase inhibitor -\> inhibits interaction of Vitamin K with factor 2, 7, 9, 10, protein C
33
What does enoxaparine do?
inhibits ONLY factor 10 activation
34
apart from PT and APTT, which paramteres of coagulation can be measured and what do they imply?
* **AT -** if low: risk for increased clotting, caused by GI or renal losses, consumption with hypercoagulability * **platelet count** (decreased prod, increased destruction, incr consumption) * **D-Dimers:** if high\> increased fibrinolysis, implies hypercoagulative state * Achtung ist auch hoch in physiologischen Situationen zB Chirurgie Fibrinogen not useful bc often high bc of inflammaation
35
Name antifibrinolytics
**E-aminocaproic acid** 20-40mg/kg in 1L NaCl IV OR **3,5mg/kg/min for 15 mins, then 0,25 CRI** inhibits plasminogen activator activity and stimulates release of a-antiplasmin that inhibits plasmin directly
36
treatments for excessive thrombosis
* **LMWH:** 50IU/kg s.c. - inhibtis 10a * **Unfractionated Heparin**: enhances AT with all its consequences, 40-60IU IV/SC * **Aspirin:** prevents Txa production in platelets, 10-100mg/kg PO or 20mg/kg per rectum
37
in equine veterinary literature, patients are considered to have subclinical DIC if...
abnormalities in min 3/5 tests: * PT * aPTT * AT * fibrinogen * D-Dimer
38
Which common emergency is associated with prolonged PT time ?
different studies horses with colic: 25-58% of them have prologed PT good prognostic indicator strangulating obstructions are associted with prol PT time
39
When does thrombocytopenia occur?
* increased use: * increased clotting f.e. sepsis, hemorrhage * increased destruction * immunmediated (IgG against thromb /megakaryocytes) * infections * decreased production: * neoplasia of bone marrow * idiopathic pancytopenia (PBZ)
40
Which is the most common heriditary bleeding disorder in horses?
Hämophilia A (no factor 8) only males (females are porters) x-chromosomal rezessiv
41
Name the three systems that inhibit coagulation in the physiological state
* NO, PGI2 * heparin sulfate + antithrombin III * thrombomodulin + thrombin (2) + Protein C
42
What is the blood volume of horses
TB: 100ml/kg WB: 78ml/kg Drafts: 61ml/kg \> 6-10% of BW
43
How much loss of blood volume can horses tolerate
15% of total blood without a problem might tolerate up to 25-30%
44
what is the donkey factor and how does it influence blood donors?
donkeys and mules carry this antigen on their RBCs \>\>\> predisposes mule foals for NI similar antigen on their platelets predisposing foals for alloimmune thrombocytopenia \>\>\> donkey blood should not be given to horses horse to donkey is ok
45
which blood types are most frequently associated with transfusion reaction?
containing Anti Aa and anti Qa antibodies
46
Calculation of blood volume needed for certain decrease in PCV how much blood can a donor give ?
Blood transfusion mL = kg × 80 mL/kg × ((desired PCV − actual PCV) /donor PCV) ~ **20% of the donor’s blood volume** (8 L in a 500- kg horse) every 30 days (give replacement if more than 15%)
47
how do you store blood prior to use?
blood bags containing 3.2% sodium citrate at a blood-to-anticoagulant ratio of 9:1. If blood is to be stored, citrate-phosphate-dextrose with adenine (CPDA) should be used and blood kept at 4 degrees
48
How long do RBCs survive after autologous transfer allogeneic transfer mild to mod crossmatch reaction
autologous transfer: 3 monate allogeneic transfer: mean halflife of 30d mild to mod crossmatch reaction: mild: 11d half life mod: 5 days half life
49
Can horses get allergic to certain blood donors post transfusion?
**The most antigenic group appears to be Aa**, with all Aa-negative horses developing antibodies if transfused with Aa-positive RBCs; _those persisted for over a year._ _Antibodies against other RBC antigens develop infrequently,_ _don't seem to appear before 1 week post transfusion_ can be detected **1** to 154 weeks after transfusion, and might disappear again after 4 weeks
50
how quick can you transfuse?
begin slowly at **0.1 mL/kg for the first 15 minutes** checking vital parameters every 5 minutes. If no adverse reactions are observed, 20 mL/kg/hr, checking vital parameters every 10 to 15 minutes
51
how often do adverse effects appear after blood transfusion and what are those? When and how should they be treated?
16% of horses 87.5% in crossmatchincompatible transfusions * hemolysis instantly-24hours after trans * fever * type 1 hypersens reactions * if severe, possible treatments: * antihistamines (hydroxyzine 0.5–1.0 mg/kg PO q12h), * dexamethasone 0.1 mg/kg intravenously [IV]) * epinephrine (0.01–0.02 mL/kg of a 1:1000 solution IV; 5–10 mL for a 500-kg horse)
52
autologous blood transfusion from body cavitiy what do I need to do differnetly?
blood-to-anticoagulant ratio of **15:1** (0.07 mL/mL of blood) instead of 9:1 blood in contact with serosal surfaces for longer than 1 hour becomes defibrinated and platelets and coag factors decrease
53
Hemoglobin-based oxygen carriers
can be used for short term if no blood available in horses (11–16 mL/kg) a foal (22 mL/kg) half life: 1,3-12 hours
54
when do horses actively bleed from thrombocytopenia?
less than 30,000 to 50,000/μL is likely to be associated with clinical signs such as petechiae or epistaxis. below 10,000/μL, active hemorrhage such as prolonged bleeding after venipuncture or hematoma formation frequently occurs clinical signs often stabilize if you go back up to 15-30
55
how to prepare and transfuse platelets? can it be stored? how much can thrombo number go up approximately?
platelets remain in suspension when RBCs are allowed to settle by gravity as is commonly done for preparation of fresh equine plasma =\> platelet rich plasma store at 22C (under 15: dysfunction) when agitated might be stored for 5 days but bac??? extrapolation from dogs: 5L (10ml/kg) fresh whole blood for 500kg horse increases platelets by 10 000/ul
56
How can the reason for intraab bleeding be established? should you go to sx?
U/S in 25% to 42% of cases an etiology cannot be established if bleeding continues or recurs despite medical management or if the origin is surgical: retrospective study: 19% detected origin during sx about 42-57% of surgically managed horses survived
57
How much plasma does a horse need to increase TP?
~ 2g/L increase through 1L Plasma 500-kg requires approx 4 to 5 L of plasma to increase TP by 10 g/L. calculation: Volume (L) = ([TP desired increase] × 0.05 × [kg]) ÷ TP Donor
58
what is the difference between fresh frozen or just frozen plasma?
fresh: plasma separated from blood within 8 hours of collection and stored at −18°C for up to 1 year. if longer than 1 year: frozen
59
Reaction to commercial vs non commercial plasma
Reactions to **commercial plasma** have a reported incidence of 8.7% in foals and 0% in adults, while the incidence with **noncommercial plasma is 10%**
60
most common causes for hemothorax
* In foals: rib fractures * adult horses: * trauma, * neoplasm, * iatrogenic injury, * strenous treadmill exercise
61
occult fecal blood measurment in horses?
new lateral flow immunoassay (SUCCEED Equine Fecal Blood Test) detecting equine hemoglobin at concentrations of 5 to 10 μg/g of feces (is positive 24-48 hours after rectal exam) only really useful to rule out
62
when is phenylephrine a risk factor for bleeds?
**64-times higher risk** for phenylephrine-associated bleeding was identified for **horses ≥15 years** old prepare blood transfucion immediately even if only tiny bleeding (more is coming)
63
Renal hemorrhage severe enough to cause anemia has been reported in horses with
pyelonephritis (four of seven horses were Arabians), **idiopathic hematuria**, and renal pseudoaneurysm in an Arabian colt
64
which drugs might induce immune mediated hemolytic anemia?
Penicillin low titers of anti–penicillin antibodies of the immunoglobulin M (IgM) class were present in 77% of horses tested. doxycycline = also a suspect
65
Treatment of IMHA refractory to corticosteroids
azathioprine (3.0 mg/kg PO q 24 h) immunsuppressiv, verwendet bei Organtransplantationen
66
Alloimmune Neonatal Neutropenia which breed in the literature? Treatment?
reported in a **Thoroughbred and an Arabian colt.** The pathophysiology is presumed to be similar to neonatal isoerythrolysis, but the disease appears to be comparatively **rare.** single injection of **G-CSF (3.5–6 μg/ kg SC)** resulted in a considerable increase in peripheral neutrophils **granulozyten-Kolonie stimulierender Faktor**
67
What is Evans Syndrome
characterized by the **simultaneous presence** of * IMHA, * thrombocytopenia, and/or * leukopenia in the absence of a known underlying cause **rare**, and few cases have been published in horses
68
What is the cause of equine infectious anemia?
equine infectious anemia (EIA) virus (lentivirus) Virus replication occurs in * monocytes, * dendritic cells, * tissue macrophages, and * endothelial cells
69
Can EIA be cured?
Once infected, horses remain lifelong carriers. Transmission occurs naturally via blood-feeding insects, particularly Tabanidae (horse and deer flies) or blood-contaminated instruments or needles.
70
Which are the hallmark signs of EIA?
**Fever and thrombocytopenia** are considered to be the most reliable clinical indicators but are far from pathognomonic for EIA **Depression, weakness, hemorrhage, peripheral edema, and weight loss** are commonly seen in the chronic form but can also accompany the acute stages.
71
72
EIA: Time from infection to seroconversion
varies widely depending on viral dose, virus strain, and test used (between **21 and 180** days).
73
How to detect EIA? Whihc
outbreak in Ireland: **specific PCR and RT-PCR assays** * _detection of Proviral DNA integrated into the host cell_ * _detection of viral RNA_ by RT-PCR detection in all tissues, _nasal secretions, and genital swabs_, and RNA was also detected in saliva. **BLOOD testing:** **agar gel immunodiffusion assay (AGID; Coggins test)** is still most widely used test and detects antibodies against the _major core protein p26._ **100% of seropositive horses detected by serum PCR** **52% of those detected by RT-PCR**
74
Causes of Piroplasmosis/Babesiosis
equine-specific hemoprotozoa: **Babesia caballi** and **Theileria** (previously Babesia) **equi**
75
Is Piroplasmosis/Babesiosis a lifelong disease?
Carrier state in untreated horses is _lifelong for T. equi_ whereas _B. caballi can be cleared_ from the horse. As the carrier status **protects against active disease and reinfection**, elimination of the parasite is not desired in endemic areas.
76
77
The most sensitive test for chronic infection with Babesia/Theileria is
EMA (equi merozoite antigens) 1 and 2 detecting cELISA
78
Treatment of Babesiosis/Piro
supportive _in endemic areas:_ no specific treatment bc carrier status is protective against reinfection _in non-endemic areas:_ **Imidocarb** diproprionate (2.2–4.4 mg/kg IM once or q 72 h for 4 doses) alongside with butylscopolamine to prevent of anticholinergic effects
79
Which are the most common clinical manifestations of Leptospirosis
very unspecific: * equine recurrent uveitis, * abortion, * stillbirth or * premature birth, * neonatal disease, and * renal failure RARELY: anemia and bleeding in foals pulmonary hemorrhage in adults
80
Which cells are infected in Babesiosis/Piroplasmosis?
_B. caballi_ directly invades _erythrocytes_ whereas the first developmental stage of T. equi takes place in _leukocytes._
81
Hemotropic Mycoplasma Infection
reported in germany infects erythrocytes of horses, dogs, cats, pigs, cattle clinical significance unknown, might cause weight loss, depression, and mild anemia PCR test Treatment: tetracyclines or fluoroquinolones
82
What is methemoglobinemia
Oxidants can damage erythrocytes by _oxidizing the heme iron in hemoglobin from Fe2+ to Fe3+_, forming **methemoglobin** and leading to anemia -\> methemoglobinemia (also other cause fe toxic)
83
Experimental feeding at the maximal voluntary intake of garlic resulted in... 0.25 g/kg PO q 12 h -\>\> 250g/d/500kg horse
_mild anemia_ (decrease of PCV from mean 36% to 28%) with _increased Heinz body formation._ excessive sweating