What Can Be Measured — and When It Starts Showing

THE CARCO STRESS MODEL: Carbon Monoxide Exposure → Peroxynitrite Formation in Capillaries → Fibrin Amyloid Formation → Microvascular Obstruction → Reduced Mitochondrial Oxygen Availability → Aerobic Energy Production Failure → Systemic Dysfunction

What This Page Explains

Fibrin amyloid structures may obstruct the smallest blood vessels, reduce oxygen availability in tissues, and disrupt cellular energy production. The resulting abnormalities are dynamic, unevenly distributed, and often most visible when blood flow or energy demand changes.

The tests and examinations described on this page do not all identify fibrin amyloid microclots directly. However, research indicates that they may reveal findings consistent with microvascular obstruction, impaired tissue oxygen availability, abnormal fibrin turnover, platelet activation, altered metabolic regulation, or disturbed energy production.

No single result confirms the entire mechanism. Findings become more meaningful when several measurements point toward the same physiological disturbance.

Why Standard Tests May Miss It

Most routine tests are:

• Static — measured at one moment
• Performed at rest — without increased physiological demand
• Designed to detect established disease rather than load-dependent dysfunction

This condition can be:

• Dynamic
• Unevenly distributed between tissues
• Dependent on blood flow and energy demand
• More visible during exertion or recovery

Testing performed only at rest may fail to reveal dysfunction that becomes visible when physical activity increases tissue oxygen and energy requirements.

What Can Be Measured by Stage

The following measurements may reveal different consequences of microvascular obstruction and impaired tissue oxygen availability. The stages may overlap, and not every person will show the same findings.

Stage Key

🟢 Early Stage
Functional instability may begin while most routine tests remain normal.

🟡 Active Exposure and Microvascular Stage
Carbon monoxide exposure, neutrophil activation, platelet activity, fibrin turnover, or impaired microvascular blood flow may become measurable.

🟠 Energy Metabolic Dysfunction Stage
Compensatory changes may begin to affect insulin regulation, intracellular mineral balance, and energy-dependent cellular functions.

🔵 Bioenergetic and Recovery-Failure Stage
Glycolytic dependence and impaired energy recovery may become visible during or after physiological stress.

🔴 Later Stage
Conventional metabolic abnormalities and clinically recognized diseases may begin to appear.

Patient-Directed Testing Without Referral

Some laboratory tests can be ordered directly through private laboratories. These measurements cannot identify fibrin amyloid microclots by themselves, but they may reveal abnormalities associated with vascular stress, altered coagulation, impaired metabolic regulation, or reduced physiological compensation.

Phase-by-Phase Breakdown of Measurements

🟢 1. Early Stage: Unexplained Blood Pressure Elevation

Possible finding: Elevated or unstable blood pressure without an otherwise clear explanation.

Microvascular obstruction increases resistance to blood flow within the smallest vessels. The body may compensate by increasing vascular tone, heart rate, or blood pressure to maintain circulation and tissue perfusion.

An unexplained increase in blood pressure does not prove the presence of fibrin amyloid microclots. However, it may be an early indication that the circulatory system is compensating for increased microvascular resistance.

Low Ferritin Without Anemia

Possible finding: Low ferritin with normal hemoglobin, without anemia. 

Low ferritin may appear at an early stage as iron stores are continuously depleted. Iron is repeatedly drawn from storage for new heme formation, while disrupted heme recycling prevents normal recovery of that iron. At the same time, iron is diverted into abnormal fibrin amyloid formation instead of returning to normal storage.

Ferritin may therefore fall after exposure begins and remain persistently low while these processes continue.

🟡 2. Active Exposure and Microvascular Stage

Possible biomarkers: MPO, platelet count, D-dimer

Myeloperoxidase — Increased MPO without other inflammation markers

Carbon monoxide exposure can activate circulating neutrophils and increase the release of myeloperoxidase into the vascular environment.

An increased plasma MPO level may therefore be most relevant during active or recent carbon monoxide exposure. MPO may rise because neutrophils release more of their stored MPO, even when the total neutrophil count does not increase.

A normal MPO level measured after exposure has ended does not exclude an earlier exposure-related response.

Platelets

Platelet activation and fibrin amyloid microclots have been reported together in conditions such as Long COVID and ME/CFS.

The platelet count may be elevated, high-normal, or completely normal because the number of platelets does not directly measure their activation state. A normal platelet count therefore does not exclude platelet hyperactivation.

D-Dimer

D-dimer is produced when cross-linked fibrin is broken down. An elevated D-dimer indicates that fibrin formation and breakdown are occurring somewhere in the body.

D-dimer does not measure the amount of fibrin amyloid microclots directly. It may rise if these structures are being broken down, but it may remain normal if they resist fibrinolysis or if their breakdown produces little measurable D-dimer.

It is not yet established how reliably fibrin amyloid microclot formation or degradation affects routine D-dimer measurements. A normal D-dimer therefore does not exclude their presence.

🟠 3. Energy Metabolic Dysfunction Stage

Possible biomarkers: RBC magnesium, fasting insulin, HOMA-IR

RBC Magnesium

Magnesium is required for ATP-dependent cellular functions. When cellular energy availability becomes inadequate, energy-dependent transport and maintenance of intracellular mineral balance may become impaired.

RBC magnesium may provide information about intracellular magnesium status that is not visible in serum magnesium. However, it is not a direct measurement of tissue energy production or fibrin amyloid microclots.

Fasting Insulin

Fasting insulin may rise before fasting glucose or HbA1c becomes abnormal. Increased insulin secretion allows the body to maintain normal blood glucose despite developing insulin resistance.

An elevated fasting insulin level may therefore reveal early metabolic compensation that is missed when only glucose or HbA1c is measured.

HOMA-IR

HOMA-IR combines fasting insulin and fasting glucose to estimate insulin resistance. It may become elevated while fasting glucose remains within the reference range.

🔵 4. Bioenergetic and Recovery-Failure Stage

Possible finding: Elevated lactate during light exertion or delayed lactate clearance after exertion.

Fibrin amyloid microclots can reduce oxygen availability in working tissues. Resting energy requirements may still be met, but physical activity rapidly increases the need for oxygen and ATP.

When oxygen availability cannot meet this demand, cells depend more heavily on glycolysis. Lactate may rise unusually early during light activity or remain elevated for longer during recovery.

An exertional lactate test may therefore reveal a load-dependent energy-production problem that is not visible in a resting lactate measurement.

🔴 5. Later Stage: Chronic Metabolic Abnormalities

Possible biomarkers: HbA1c, fasting glucose, fasting insulin, lipid panel

HbA1c and Fasting Glucose

Long-term insulin resistance may eventually exceed the body’s ability to maintain normal blood glucose. Fasting glucose and HbA1c may then begin to rise.

These are relatively late markers. Normal HbA1c does not exclude elevated fasting insulin, compensatory hyperinsulinemia, or earlier energy metabolic dysfunction.

Lipid Panel

Insulin resistance and altered energy metabolism can affect hepatic lipid processing. Possible findings include elevated triglycerides, reduced HDL cholesterol, increased LDL cholesterol, or other changes in the lipid profile.

A lipid panel shows the downstream metabolic consequences but does not identify their underlying cause.

Clinical and Specialized Testing

These examinations require clinical equipment, specialist assessment, or a medical referral. They may reveal impaired microvascular flow, abnormal tissue perfusion, reduced tissue oxygen availability, or disturbed energy recovery.

Microvascular Blood Flow and Perfusion

EndoPAT

EndoPAT measures changes in peripheral arterial tone during reactive hyperemia after temporary blood-flow restriction. It can reveal an impaired vascular response that may not be visible in resting laboratory tests.

The manufacturer discontinued production and sales of EndoPAT 2000 and EndoPAT X on May 1, 2025. Existing systems may remain in use, and accessories and technical support are scheduled to remain available until May 1, 2028.

Flow-Mediated Dilation — FMD

FMD uses ultrasound to measure how much an artery expands after temporary blood-flow restriction. It assesses vascular reactivity but does not directly image fibrin amyloid microclots or capillary obstruction.

Nailfold Capillaroscopy

Nailfold capillaroscopy visualizes superficial capillaries at the base of the fingernails. It can reveal changes in capillary shape, density, blood flow, or areas where capillaries are absent.

Retinal Microvascular Imaging

The retinal circulation can be examined directly through the eye.

A dilated eye examination and fundus photography may reveal hemorrhages, cotton-wool spots, vascular abnormalities, or other signs of local ischemia.

Optical coherence tomography angiography, or OCTA, visualizes blood flow in the superficial and deep retinal capillary networks. It can identify areas of reduced or absent capillary perfusion.

Fluorescein angiography can show delayed vascular filling, leakage, and retinal non-perfusion.

These examinations may provide direct evidence of impaired retinal microcirculation. They cannot by themselves determine whether an obstruction consists specifically of fibrin amyloid microclots.

Laser Speckle Imaging — LSI

Laser speckle imaging measures changes in superficial microvascular blood flow by analyzing patterns created when laser light is scattered by moving blood cells.

Laser Doppler Imaging — LDI

Laser Doppler imaging evaluates superficial tissue perfusion by measuring frequency changes in laser light reflected from moving red blood cells.

Coagulation and Fibrin Structure

Fibrin Amyloid Microclot Analysis

Specialized research methods can examine plasma for abnormal fibrin amyloid structures. These methods are not part of standard routine laboratory testing and may not be widely available clinically.

TEG and ROTEM

Thromboelastography and rotational thromboelastometry dynamically measure clot formation, clot strength, and clot breakdown. They can reveal abnormal coagulation properties but do not directly determine whether the clot structure is amyloid.

Metabolic Regulation

Oral Glucose Tolerance Test With Insulin

An OGTT with simultaneous insulin measurements shows how both glucose and insulin respond to a glucose load.

It may reveal compensatory hyperinsulinemia or insulin resistance before fasting glucose or HbA1c becomes abnormal.

Tissue Oxygen Availability and Energy Production

Cardiopulmonary Exercise Testing — CPET

CPET measures oxygen consumption, carbon dioxide production, heart rate, ventilation, and other physiological responses during exercise. It assesses the integrated ability of circulation, respiration, and tissues to support increasing energy demand.

Two-Day CPET

A two-day CPET can identify impaired recovery when exercise capacity or oxygen consumption declines abnormally on the second day. This may be particularly relevant when post-exertional malaise is a central symptom.

VO₂ Max

VO₂ max estimates maximal aerobic capacity. A reduced value shows limited whole-body aerobic performance but does not identify the precise location or cause of the limitation.

Near-Infrared Spectroscopy — NIRS

NIRS uses near-infrared light to estimate local tissue oxygenation. It can provide information about oxygen delivery, extraction, and recovery in a specific tissue such as skeletal muscle.

Phosphorus-31 Magnetic Resonance Spectroscopy — ³¹P-MRS

³¹P-MRS measures high-energy phosphate metabolism inside tissues. It can evaluate phosphocreatine depletion and recovery, providing information about cellular energy production and post-exertional recovery.

Lactate Response Testing

Blood lactate can be measured before, during, and after controlled exertion. An unusually early rise or delayed clearance may indicate increased glycolytic dependence caused by inadequate tissue oxygen availability.

Lactate-to-Pyruvate Ratio

The lactate-to-pyruvate ratio provides information about the relationship between these two metabolic compounds. It may help characterize altered metabolism but does not directly measure fibrin amyloid microclots or tissue perfusion.

Blood Gases and Circulatory Testing

Arterial and Venous Blood Gas Testing — ABG and VBG

Blood gas testing measures oxygen- and carbon-dioxide-related values and acid–base balance in the sampled blood. Normal arterial oxygenation confirms that oxygen has entered arterial blood. It does not prove that blood reaches every capillary or that individual tissues receive enough oxygen.

Invasive Cardiopulmonary Exercise Testing — iCPET

iCPET combines exercise testing with invasive measurements of cardiac pressures, blood flow, and oxygen extraction.

It can help distinguish between limitations in circulation, cardiac output, oxygen delivery, and tissue oxygen extraction during exertion.

Regional Perfusion and Metabolic Imaging

Perfusion MRI

Perfusion MRI evaluates regional blood flow through tissues and may reveal areas with reduced perfusion.

SPECT

SPECT uses radioactive tracers to visualize regional blood flow and tissue activity in organs such as the brain and heart.

PET

PET uses radiotracers to examine regional metabolism, blood flow, or specific molecular processes depending on the tracer used.

Direct Tissue Oxygenation Monitoring

Specialized methods can measure oxygen availability within tissues. These measurements can reveal an imbalance between local oxygen delivery and tissue demand that is not visible in arterial blood oxygen values.

Interpretation

None of these tests alone proves that fibrin amyloid microclots are responsible for a person’s symptoms.

However, a combination of findings—such as impaired microvascular perfusion, platelet activation, altered fibrin turnover, abnormal exertional lactate, reduced tissue oxygenation, elevated fasting insulin, or delayed energy recovery—may provide objective evidence of the physiological disturbances expected when the microcirculation is obstructed.

Normal resting tests do not necessarily exclude a problem that is unevenly distributed, load-dependent, or visible only during exertion and recovery.

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