Management of patients with acute hemorrhage requires addressing the source of bleeding, replenishing blood volume, and addressing any coagulopathy that may be present. Assessing coagulopathy and predicting blood requirements in real-time in patients experiencing ongoing bleeding can pose substantial challenges. In these patients, transfusion concepts based on ratios do not effectively address coagulopathy or reduce mortality. Moreover, ratio-based concepts do not stop bleeding; instead, they just give physicians more time to identify the bleeding source and plan management strategies. In clinical practice, standard laboratory coagulation tests (SLCT) are frequently used to assess various aspects of blood clotting. However, these tests may not always offer a comprehensive understanding of clinically significant coagulopathy and the severity of blood loss. Furthermore, the SLCT have a considerable turnaround time, which may not be ideal for making prompt clinical decisions. In recent years, there has been a growing interest in point-of-care viscoelastic assays like rotational thromboelastometry, which provide real-time, dynamic information about clot formation and dissolution.

• Bleeding
• Critical care
• Haemorrhage
• Intensive care unit
• Rotational thromboelastometry
• Viscoelastic tests

• Acute kidney injury
• Albumin
• Balanced electrolyte solution
• Coagulopathy
• Endothelial glycocalyx
• Hyperchloremic metabolic acidosis
• Immunologic reaction

• disseminated intravascular coagulation
• fetal death
• fibrinogen
• maternal prognosis
• placental abruption

• fluid compartments
• monitoring
• novel fluids
• perfusion
• physiology
• volume kinetics

• hemostasis
• plasma
• transfusion
• traum

• Coagulopathy
• Colloid
• Crystalloid
• Resuscitation
• Transfusion
• Trauma

Synthetic colloids are commonly administered to dogs to treat absolute or relative hypovolaemia. Voluven^® (tetrastarch 130/0.4) and Gelofusine^® (succinylated gelatin) are available to veterinarians in South Africa. In humans, use of these products has caused acid–base derangements, changes in haematology and impaired haemostasis. We aimed to investigate these effects in healthy normovolaemic dogs. Eight healthy adult beagle dogs underwent a cross-over study, receiving Voluven^® or Gelofusine^® (10 mL/kg/h for 120 min) once each with a 14-day washout between treatments. Dogs were premedicated with dexmedetomidine (10 µg/kg intramuscularly). Anaesthesia was induced with propofol and the dogs were maintained with isoflurane-in-oxygen. The anaesthetised dogs were connected to a multi-parameter monitor to monitor physiological parameters throughout. Catheters placed in a jugular vein and dorsal metatarsal artery allowed sampling of venous and arterial blood. Blood was collected immediately prior to commencement of colloid infusion, after 60 min infusion and at the end of infusion (120 min) to allow for arterial blood gas analysis, haematology and coagulation testing (activated partial thromboplastin time [aPTT], prothrombin time [PT] and thromboelastography [TEG]). There was no effect, between treatments or over time, on blood pH. The haemoglobin concentration, erythrocyte count and haematocrit decreased significantly over time (all p < 0.01), with no differences between treatments, and remained within normal clinical ranges. There were no differences between treatments or over time for the TEG, aPTT and PT tests of haemostasis. At the dose studied, Voluven^® and Gelofusine^® had comparably negligible effects on blood acid–base balance and coagulation in normovolaemic dogs.

• Gelofusine
• Voluven
• acid–base balance
• coagulation
• complete blood count (CBC)
• full blood count (FBC)
• synthetic colloids

• fluid therapy
• point prevalence study
• pre-operative medicine
• risk

• Adult
• Aged
• Colloids/therapeutic use
• Cross-Sectional Studies
• Crystalloid Solutions/therapeutic use
• Female
• Fluid Therapy/methods
• Fluid Therapy/standards
• Fluid Therapy/statistics & numerical data
• Humans
• Intraoperative Care/methods
• Intraoperative Care/standards
• Intraoperative Care/statistics & numerical data
• Male
• Middle Aged
• Poland
• Prevalence

• HES
• colloid
• fluid therapy
• horse
• hypoalbuminemia
• resuscitation

• Trauma-induced coagulopathy
• coagulation management in trauma
• damage control resuscitation (DCR)
• directed coagulation therapy
• hemostatic control in acute trauma

The current study aimed to measure the effects of Plasma-Lyte 148 solution on the blood coagulation profile according to the hemodilution level using rotational thromboelastometry (ROTEM) tests. Venous blood was collected from 12 healthy volunteers and divided into four specimen bottles, which were diluted at different levels with Plasma-Lyte 148 (0, 20, 40, and 60%). Following this, ROTEM tests were performed on the study samples. We found that as the hemodilution level increased, the ROTEM values showed a hypocoagulable pattern. The change rate of the maximum clot firmness (MCF) of INTEM was greater in the 40 (P = 0.015) and 60% (P < 0.001) dilutions than it was in the 20% dilution. Greater lengthening of the clot formation time of EXTEM was observed in the 60% dilution than it was in the 20% dilution (P < 0.001). The alpha-angle of EXTEM showed a greater decrease in the 60% dilution than it did in the 20% dilution (P < 0.001). A larger change rate of the MCF of EXTEM was observed in the 40 (P = 0.003) and 60% (P < 0.001) dilutions than it was in the 20% dilution. A greater decrease in the MCF of FIBTEM was identified in the 40 (P = 0.009) and 60% (P < 0.001) dilutions than in the 20% dilution. All coagulation pathways exhibited hypocoagulable patterns as the hemodilution level increased. However, most of the mean values of ROTEM parameters were within the normal reference range, except for those of the 60% dilution.

Tetrastarch solution (TS) can impair coagulation but the clinical relevance of this impairment is unclear in veterinary medicine.

Compare the effects of volume replacement (VR) with lactated Ringer's solution (LRS) or 6% TS on coagulation in hemorrhaged dogs.

Six healthy English Pointer dogs (19.7‐35.3 kg).

Prospective crossover study. Dogs were anesthetized without hemorrhage and VR (control). Two weeks later, dogs were hemorrhaged under anesthesia on 2 occasions (8‐week washout intervals) and randomly received VR with LRS or TS at 3:1 or 1:1 of shed blood, respectively, aiming to decrease the hematocrit to 33%. Rotational thromboelastometry and other coagulation variables were determined before 0.5, 2, and 4 hours after VR during anesthesia and 24 hours after VR (conscious dogs).

Buccal mucosal bleeding time did not differ between treatments after VR. Activated partial thromboplastin time increased from controls 4 hours after TS (P = 0.045). Clot formation time (CFT) and alfa‐angle increased from controls from 0.5 to 4 hours after LRS (CFT, P ≤ 0.0001‐0.02; alpha angle, P = 0.0001‐0.02) and from 0.5 to 2 hours after TS (CFT, P = 0.0002‐0.01; alpha angle, P = 0.0005‐0.02). The maximum clot firmness decreased from controls from 0.5 to 4 hours after LRS (P ≤ 0.0001‐0.01) and TS (P ≤ 0.0001‐0.04).

Tetrastarch does not impair primary hemostasis and induces transient dilutional coagulopathy that is similar to LRS because, when compared to a 3 times higher volume of LRS in hemorrhaged dogs, it does not cause greater interference on the viscoelastic properties of the coagulum.

• coagulation
• colloids
• crystalloids
• hydroxyethyl starch
• thromboelastometry

• REBOA
• blood
• plasma
• resuscitation
• thoracotomy
• transfusions
• wholeblood

• Acidosis/prevention & control
• Blood Coagulation Disorders/prevention & control
• Hemorrhage/prevention & control
• Humans
• Hypothermia/prevention & control
• Practice Guidelines as Topic
• Resuscitation/methods
• Resuscitation/trends
• Shock, Hemorrhagic/prevention & control

• T32 GM008315 NIGMS NIH HHS

• Colloid
• crystalloid
• fibrinogen
• hypertonic saline
• maximum clot firmness

Damage control resuscitation has been increasingly adopted and practiced over the last decade. The concepts used are not new to this era of medicine but are novel in combination. This chapter will focus on adjuncts to damage control resuscitation (DCR) including massive transfusion protocols, the “other” tenets of damage control resuscitation, hypertonic saline, tranexamic acid, pharmacologic resuscitation, Factor VIIa, and prothrombin complex, and viscoelastic testing.

• PT
• biomarker
• coagulopathy
• point‐of‐care
• prothrombin
• severe bleeding

• coagulation
• factor XIII
• fibrinogen
• platelets
• surgery

Hydroxyethyl starch (HES) solutions are used for volume expansion during surgery. We aimed to investigate how 6%HES 130/0.4 affects hemostasis.

Blood samples were collected from 12 healthy adult volunteers, diluting with 6%HES 130/0.4 (HES group) or Ringer lactate solution (RL control group). The hemodilution ratio (HR) of citrated blood volume to plasma substitute volume was 10: 0 (undiluted), 10: 2, 10: 4, and 10: 6. Clotting factors activity was measured. Thrombin generation was monitored. Platelet function was analyzed.

1) Activity of coagulation factor was decreased with increasing HR compared to undiluted baseline, and the activity of FVIII was significantly decreased in HES vs. RL. 2) Calibrated automated thrombography (CAT) results showed HES extended lag time, time to peak (ttpeak), start tail, and decreased peak of thrombin generation. Although lag time and ttpeak were significantly prolonged in HES vs. RL, endogenous thrombin potential (ETP) did not change. 3) Flow cytometric (FCM) analysis showed that HES reduced platelet phospholipids serine (PS) vs. baseline and RL. 4) HES significantly decreased antithrombin activity (AT: A) of the anticoagulant system with increasing HR vs. baseline and RL. 5) For fibrinolytic system, HES did not affect fibrinogen degradation products (FDP) and D-dimers (D-D) vs. baseline, or α₂-antiplasmin (α2-AP) vs. RL.

By reducing FVIII activity and platelet PS expression, HES interfered with PS combining to FXIa, FVIIIa, and FVa, which affected the acceleration and explosion stage of thrombin. The decreased velocity and peak of thrombin generation delays and reduces clot formation. Combined 6%HES 130/0.4 decreased anticoagulant activity and may have clinical utility.

• Coagulopathy
• Cryoprecipitate
• Fibrinogen
• Fibrinogen concentrate
• Massive transfusion
• Trauma
• Viscoelastic haemostatic assays

• Coagulation management
• Coagulopathy
• Direct oral anticoagulants
• Jersey calves
• Medical implants

• coagulation
• dog
• hydroxyethyl starch
• platelet function
• thromboelastometry

• TEG
• coagulopathy
• dogs
• hemostasis
• synthetic colloids

• Factor XIII
• Fibrinogen
• Hydroxyethyl starch derivatives
• Neurosurgery
• Thromboelastography

• PFA-100
• colloids
• dog
• platelet function

• algorithms
• bleeding
• coagulopathy
• factor concentrates
• hemostasis

• Algorithms
• Blood Loss, Surgical/prevention & control
• Blood Transfusion
• Disseminated Intravascular Coagulation/diagnosis
• Disseminated Intravascular Coagulation/therapy
• Female
• Humans
• Male
• Postpartum Hemorrhage/diagnosis
• Postpartum Hemorrhage/therapy
• Practice Guidelines as Topic
• Wounds and Injuries/diagnosis
• Wounds and Injuries/therapy

Synthetic colloids are often used during fluid resuscitation and affect coagulation.

To compare the effects of an isotonic crystalloid and synthetic colloid on coagulation in healthy dogs and dogs with systemic inflammation.

Sixteen adult purpose‐bred Beagles.

Randomized, placebo‐controlled, blinded study. Dogs were randomized into one of two groups receiving fluid resuscitation with either 40 mL/kg IV 0.9% NaCl or tetrastarch after administration of lipopolysaccharide or an equal volume of placebo. After a 14‐day washout period, the study was repeated such that dogs received the opposite treatment (LPS or placebo) but the same resuscitation fluid. Blood samples were collected at 0, 1, 2, 4, and 24 hours for measurement of coagulation variables.

Administration of either fluid to healthy dogs and dogs with systemic inflammation resulted in similar increases in prothrombin time and activated clotting time. In comparison to saline administration, tetrastarch administration resulted in significantly decreased R (P = .017) in healthy dogs, as well as significantly increased activated partial thromboplastin time (P ≤ .016), CL30% (P ≤ .016), and K (P < .001) and significantly decreased platelet count (P = .019), α (P ≤ .001), MA (P < .001), and von Willebrand factor antigen (P < .001) and collagen binding activity (P ≤ .003) in both healthy dogs and dogs with systemic inflammation.

Tetrastarch bolus administration to dogs with systemic inflammation resulted in a transient hypocoagulability characterized by a prolonged activated partial thromboplastin time, decreased clot formation speed and clot strength, and acquired type 1 von Willebrand disease.

• Lipopolysaccharide
• Tetrastarch
• Thromboelastography
• von Willebrand factor

The European Medicines Agency does not recommend the use of hydroxyethyl starch-based volume replacement solutions in critically ill patients due to an increased risk of renal failure. However, this recommendation is questionable for its perioperative use. Several recent randomised controlled studies do not indicate a risk for renal failure—not even after high-risk surgery. Human albumin is used in our neurointensive care unit as a part of the “Lund concept” of brain injury resuscitation, and albumin has been introduced in elective neurosurgery instead of starch. The aim of our prospective unblinded observational cohort study was to compare the degree of dilutive coagulopathy after albumin and starch intra-operative fluid therapy.

Thirty-nine patients undergoing elective brain tumour surgery with craniotomy received either 130/0.42 hydroxyethyl starch or 5 % albumin infusions. The first 18 patients received starch, whereas the rest received albumin. Rotational thromboelastometry with ROTEM and platelet aggregometry with Multiplate were performed before surgery, after the first and second consecutive colloid infusions (250/500 ml albumin or 500/1000 ml starch) and at the end of surgery.

Both intra- and inter-group comparisons showed more deranged ROTEM parameters after the higher doses of starch. Multiplate detected changes only in the albumin group after 500-ml infusion. Blood los did not differ between groups, nor did haemoglobin preoperatively or at end of surgery. Lower volumes of albumin were required to maintain stable intra-operative haemodynamic parameters; 250/500 ml albumin corresponded to 500/1000 ml starch.

Hydroxyethyl starch affected coagulation at lower volumes, with a more prominent effect on clot structure at the end of surgery, corroborating previous research. Only albumin decreased platelet aggregation, and 5 % albumin had a more potential volume effect than 130/0.42 hydroxyethyl starch.

• Albumin
• Hydroxyethyl starch
• Neurosurgery
• Platelet aggregation
• Thromboelastography